{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T01:20:07Z","timestamp":1775438407823,"version":"3.50.1"},"reference-count":191,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,4,29]],"date-time":"2020-04-29T00:00:00Z","timestamp":1588118400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UIDB\/04046\/2020; UIDP\/04046\/2020; PTDC\/BIM-MEC\/2131\/2014; FCT\/02\/SAICT\/2017\/28800; SFRH\/PD\/BD\/114389\/2016; PD\/BD\/114393\/2016"],"award-info":[{"award-number":["UIDB\/04046\/2020; UIDP\/04046\/2020; PTDC\/BIM-MEC\/2131\/2014; FCT\/02\/SAICT\/2017\/28800; SFRH\/PD\/BD\/114389\/2016; PD\/BD\/114393\/2016"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000292","name":"Cystic Fibrosis Trust","doi-asserted-by":"publisher","award":["SRC 013"],"award-info":[{"award-number":["SRC 013"]}],"id":[{"id":"10.13039\/501100000292","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["H2020-SC1-2017-755021"],"award-info":[{"award-number":["H2020-SC1-2017-755021"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006501","name":"Cystic Fibrosis Foundation Therapeutics","doi-asserted-by":"publisher","award":["AMARAL19G0"],"award-info":[{"award-number":["AMARAL19G0"]}],"id":[{"id":"10.13039\/100006501","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>One of the key features associated with the substantial increase in life expectancy for individuals with CF is an elevated predisposition to cancer, firmly established by recent studies involving large cohorts. With the recent advances in cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies and the increased long-term survival rate of individuals with cystic fibrosis (CF), this is a novel challenge emerging at the forefront of this disease. However, the mechanisms linking dysfunctional CFTR to carcinogenesis have yet to be unravelled. Clues to this challenging open question emerge from key findings in an increasing number of studies showing that CFTR plays a role in fundamental cellular processes such as foetal development, epithelial differentiation\/polarization, and regeneration, as well as in epithelial\u2013mesenchymal transition (EMT). Here, we provide state-of-the-art descriptions on the moonlight roles of CFTR in these processes, highlighting how they can contribute to novel therapeutic strategies. However, such roles are still largely unknown, so we need rapid progress in the elucidation of the underlying mechanisms to find the answers and thus tailor the most appropriate therapeutic approaches.<\/jats:p>","DOI":"10.3390\/ijms21093133","type":"journal-article","created":{"date-parts":[[2020,4,29]],"date-time":"2020-04-29T13:23:45Z","timestamp":1588166625000},"page":"3133","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["What Role Does CFTR Play in Development, Differentiation, Regeneration and Cancer?"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0828-8630","authenticated-orcid":false,"given":"Margarida D.","family":"Amaral","sequence":"first","affiliation":[{"name":"BioISI\u2014Biosystems and Integrative Sciences Institute, Faculty of Sciences, University of Lisboa, 1749-016 Lisboa, Portugal"}]},{"given":"Margarida C.","family":"Quaresma","sequence":"additional","affiliation":[{"name":"BioISI\u2014Biosystems and Integrative Sciences Institute, Faculty of Sciences, University of Lisboa, 1749-016 Lisboa, Portugal"}]},{"given":"Ines","family":"Pankonien","sequence":"additional","affiliation":[{"name":"BioISI\u2014Biosystems and Integrative Sciences Institute, Faculty of Sciences, University of Lisboa, 1749-016 Lisboa, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1056\/NEJM199502233320803","article-title":"The risk of cancer among patients with cystic fibrosis","volume":"332","author":"Neglia","year":"1995","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1093\/jnci\/djs481","article-title":"Cancer Risk in Cystic Fibrosis: A 20-Year Nationwide Study From the United States","volume":"105","author":"Maisonneuve","year":"2013","journal-title":"JNCI J. Natl. Cancer Inst."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1073\/pnas.1914912117","article-title":"Cystic fibrosis carriers are at increased risk for a wide range of cystic fibrosis-related conditions","volume":"117","author":"Miller","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1002\/ppul.20169","article-title":"Developmental paradigm for early features of cystic fibrosis","volume":"40","author":"Larson","year":"2005","journal-title":"Pediatr. Pulmonol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2736","DOI":"10.1002\/dvdy.20912","article-title":"Cystic fibrosis transmembrane conductance regulator (CFTR) dependent cytoskeletal tension during lung organogenesis","volume":"235","author":"Larson","year":"2006","journal-title":"Dev. Dyn."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1164\/rccm.201004-0643OC","article-title":"Loss of Cystic Fibrosis Transmembrane Conductance Regulator Function Produces Abnormalities in Tracheal Development in Neonatal Pigs and Young Children","volume":"182","author":"Meyerholz","year":"2010","journal-title":"Am. J. Respir Crit. Care Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1242\/dev.091819","article-title":"Cftr controls lumen expansion and function of Kupffer\u2019s vesicle in zebrafish","volume":"140","author":"Bagnat","year":"2013","journal-title":"Development"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1038\/cdd.2016.118","article-title":"CFTR-\u03b2-catenin interaction regulates mouse embryonic stem cell differentiation and embryonic development","volume":"24","author":"Liu","year":"2017","journal-title":"Cell Death Differ."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1111\/andr.12450","article-title":"Congenital bilateral absence of the vas deferens as an atypical form of cystic fibrosis: Reproductive implications and genetic counseling","volume":"6","author":"Faucz","year":"2018","journal-title":"Andrology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1165\/ajrcmb\/7.5.485","article-title":"Differential localization of the cystic fibrosis transmembrane conductance regulator in normal and cystic fibrosis airway epithelium","volume":"7","author":"Puchelle","year":"1992","journal-title":"Am. J. Respir Cell Mol. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.1172\/JCI118199","article-title":"CFTR and differentiation markers expression in non-CF and delta F 508 homozygous CF nasal epithelium","volume":"96","author":"Dupuit","year":"1995","journal-title":"J. Clin. Invest."},{"key":"ref_12","first-page":"191","article-title":"Decreased expression of the CFTR protein in remodeled human nasal epithelium from non-cystic fibrosis patients","volume":"72","author":"Brezillon","year":"1995","journal-title":"Lab. Investig."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1172\/JCI7453","article-title":"A PDZ-interacting domain in CFTR is an apical membrane polarization signal","volume":"104","author":"Moyer","year":"1999","journal-title":"J. Clin. Investig."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1113\/jphysiol.2009.182246","article-title":"Cystic fibrosis transmembrane conductance regulator trafficking modulates the barrier function of airway epithelial cell monolayers","volume":"588","author":"LeSimple","year":"2010","journal-title":"J. Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1183\/09059180.05.00009702","article-title":"In vivo models of human airway epithelium repair and regeneration","volume":"14","author":"Coraux","year":"2005","journal-title":"Eur. Respir. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1002\/path.2118","article-title":"Human airway surface epithelial regeneration is delayed and abnormal in cystic fibrosis","volume":"211","author":"Hajj","year":"2007","journal-title":"J. Pathol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"C912","DOI":"10.1152\/ajpcell.00215.2010","article-title":"Cystic fibrosis transmembrane conductance regulator is involved in airway epithelial wound repair","volume":"299","author":"Schiller","year":"2010","journal-title":"Am. J. Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2961","DOI":"10.1016\/j.bbamcr.2013.07.021","article-title":"Downregulation of CFTR promotes epithelial-to-mesenchymal transition and is associated with poor prognosis of breast cancer","volume":"1833","author":"Zhang","year":"2013","journal-title":"Biochim. Biophys. Acta - Mol. Cell Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.ygeno.2015.07.005","article-title":"Transcriptome meta-analysis reveals common differential and global gene expression profiles in cystic fibrosis and other respiratory disorders and identifies CFTR regulators","volume":"106","author":"Clarke","year":"2015","journal-title":"Genomics"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2234","DOI":"10.1016\/j.bbamcr.2016.05.012","article-title":"A novel regulatory role for tissue transglutaminase in epithelial-mesenchymal transition in cystic fibrosis","volume":"1863","author":"Nyabam","year":"2016","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1186\/s12931-018-0834-8","article-title":"Epithelial mesenchymal transition (EMT): A universal process in lung diseases with implications for cystic fibrosis pathophysiology","volume":"19","author":"Farrow","year":"2018","journal-title":"Respir. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1016\/j.cub.2019.12.025","article-title":"Osmotic Gradients in Epithelial Acini Increase Mechanical Tension across E-cadherin, Drive Morphogenesis, and Maintain Homeostasis","volume":"30","author":"Narayanan","year":"2020","journal-title":"Curr. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1111\/j.1440-1843.2011.01994.x","article-title":"Promoter hypermethylation of the CFTR gene and clinical\/pathological features associated with non-small cell lung cancer","volume":"16","author":"Son","year":"2011","journal-title":"Respirology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1016\/j.bbamcr.2013.12.013","article-title":"Disrupted interaction between CFTR and AF-6\/afadin aggravates malignant phenotypes of colon cancer","volume":"1843","author":"Sun","year":"2014","journal-title":"Biochim. Biophys. Acta - Mol. Cell Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"76955","DOI":"10.18632\/oncotarget.12762","article-title":"CFTR is a potential marker for nasopharyngeal carcinoma prognosis and metastasis","volume":"7","author":"Tu","year":"2016","journal-title":"Oncotarget"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Zhang, J., Wang, Y., Jiang, X., and Chan, H.C. (2018). Cystic fibrosis transmembrane conductance regulator\u2014Emerging regulator of cancer. Cell Mol. Life Sci.","DOI":"10.1007\/s00018-018-2755-6"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1093\/hmg\/2.3.213","article-title":"Expression of the cystic fibrosis gene in human foetal tissues","volume":"2","author":"Trezise","year":"1993","journal-title":"Hum. Mol. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1165\/ajrcmb.10.4.7510983","article-title":"Regional expression of CFTR in developing human respiratory tissues","volume":"10","author":"Tizzano","year":"1994","journal-title":"Am. J. Respir Cell Mol. Biol"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1203\/00006450-199408000-00002","article-title":"Immunohistochemical Localization of Cystic Fibrosis Transmembrane Conductance Regulator in Human Fetal Airway and Digestive Mucosa","volume":"36","author":"Gaillard","year":"1994","journal-title":"Pediatr. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1242\/dev.113.1.305","article-title":"Expression of the cystic fibrosis gene in human development","volume":"113","author":"Harris","year":"1991","journal-title":"Development"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1093\/hmg\/2.3.219","article-title":"Cell-specific localization of CFTR mRNA shows developmentally regulated expression in human fetal tissues","volume":"2","author":"Tizzano","year":"1993","journal-title":"Hum. Mol. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1016\/S0016-5085(97)70187-2","article-title":"The cystic fibrosis transmembrane conductance regulator as a marker of human pancreatic duct development","volume":"113","author":"Hyde","year":"1997","journal-title":"Gastroenterology"},{"key":"ref_33","first-page":"F723","article-title":"Developmental regulation of CFTR expression during human nephrogenesis","volume":"271","author":"Devuyst","year":"1996","journal-title":"Am. J. Physiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1093\/hmg\/11.2.125","article-title":"Temporal regulation of CFTR expression during ovine lung development: Implications for CF gene therapy","volume":"11","year":"2002","journal-title":"Hum. Mol. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1002\/ppul.20690","article-title":"Evolution of CFTR protein distribution in lung tissue from normal and CF human fetuses","volume":"42","author":"Marcorelles","year":"2007","journal-title":"Pediatr. Pulmonol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1165\/ajrcmb\/8.2.201","article-title":"Cystic Fibrosis Gene and Protein Expression during Fetal Lung Development","volume":"8","author":"McGrath","year":"1993","journal-title":"Am. J. Respir. Cell Mol. Biol"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/S0140-6736(84)90765-7","article-title":"Fetal Abnormalities in Cystic Fibrosis Suggest a Deficiency in Proteolysis of Cholecystokinin","volume":"324","author":"Gosden","year":"1984","journal-title":"Lancet"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1002\/ajmg.1320280420","article-title":"Pathological confirmation of cystic fibrosis in the fetus following prenatal diagnosis","volume":"28","author":"Ornoy","year":"1987","journal-title":"Am. J. Med. Genet."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3231","DOI":"10.1113\/jphysiol.2008.150763","article-title":"Congenital tracheal malformation in cystic fibrosis transmembrane conductance regulator-deficient mice","volume":"586","author":"Bonvin","year":"2008","journal-title":"J. Physiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0091253","article-title":"Characterization of defects in ion transport and tissue development in Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)-knockout rats","volume":"9","author":"Tuggle","year":"2014","journal-title":"PLoS ONE"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1038\/s41374-018-0026-7","article-title":"Lack of cystic fibrosis transmembrane conductance regulator disrupts fetal airway development in pigs","volume":"98","author":"Meyerholz","year":"2018","journal-title":"Lab. Investig."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-213X-5-2","article-title":"Pathophysiologic consequences following inhibition of a CFTR-dependent developmental cascade in the lung","volume":"5","author":"Cohen","year":"2005","journal-title":"BMC Dev. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1006\/mgme.1998.2683","article-title":"Molecular Pathophysiology of Cystic Fibrosis Based on the Rescued Knockout Mouse Model","volume":"64","author":"Cohen","year":"1998","journal-title":"Mol. Genet. Metab."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1152\/ajplung.2000.279.2.L333","article-title":"CFTR modulates lung secretory cell proliferation and differentiation","volume":"279","author":"Larson","year":"2000","journal-title":"Am. J. Physiol. - Lung Cell Mol. Physiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1006\/mgme.1998.2755","article-title":"Modification of Development by the CFTR Genein Utero","volume":"65","author":"Morrow","year":"1998","journal-title":"Mol. Genet. Metab."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1006\/mthe.2000.0209","article-title":"Gene transfer into the fetal primate: Evidence for the secretion of transgene product","volume":"2","author":"Larson","year":"2000","journal-title":"Mol. Ther."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1007\/BF03343794","article-title":"The cystic fibrosis transmembrane regulator gene and male infertility","volume":"23","author":"Quinzii","year":"2000","journal-title":"J. Endocrinol. Invest."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1093\/humupd\/dms027","article-title":"Regulation of male fertility by CFTR and implications in male infertility","volume":"18","author":"Chen","year":"2012","journal-title":"Hum. Reprod. Update"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.morpho.2018.11.001","article-title":"Update on the cellular and molecular aspects of cystic fibrosis transmembrane conductance regulator (CFTR) and male fertility","volume":"103","author":"Yefimova","year":"2019","journal-title":"Morphologie"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1056\/NEJM196807112790203","article-title":"Reproductive Failure in Males with Cystic Fibrosis","volume":"279","author":"Kaplan","year":"1968","journal-title":"N. Engl. J. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1794","DOI":"10.1001\/jama.1992.03480130110034","article-title":"Congenital Bilateral Absence of the Vas Deferens","volume":"267","author":"Anguiano","year":"1992","journal-title":"JAMA"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1016\/S0022-5347(01)64278-2","article-title":"Normal vas deferens in fetuses with cystic fibrosis","volume":"158","author":"Gaillard","year":"1997","journal-title":"J. Urol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/j.humpath.2011.04.031","article-title":"Cystic fibrosis transmembrane conductance regulator protein expression in the male excretory duct system during development","volume":"43","author":"Marcorelles","year":"2012","journal-title":"Hum. Pathol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1016\/0140-6736(90)92066-Q","article-title":"Abnormal distribution of CF \u0394F508 allele in azoospermic men with congenital aplasia of epididymis and vas deferens","volume":"336","author":"Dumur","year":"1990","journal-title":"Lancet"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1056\/NEJM199302113280619","article-title":"High Frequency of the R117H Cystic Fibrosis Mutation in Patients with Congenital Absence of the Vas Deferens","volume":"328","author":"Gervais","year":"1993","journal-title":"N. Engl. J. Med."},{"key":"ref_56","first-page":"272","article-title":"Is congenital bilateral absence of vas deferens a primary form of cystic fibrosis? Analyses of the CFTR gene in 67 patients","volume":"56","author":"Mercier","year":"1995","journal-title":"Am. J. Hum. Genet."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1002\/1098-1004(200008)16:2<143::AID-HUMU7>3.0.CO;2-J","article-title":"Spectrum of CFTR mutations in cystic fibrosis and in congenital absence of the vas deferens in France","volume":"16","author":"Claustres","year":"2000","journal-title":"Hum. Mutat."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1186\/rr82","article-title":"\u2018CFTR-opathies\u2019: Disease phenotypes associated with cystic fibrosis transmembrane regulator gene mutations","volume":"2","author":"Noone","year":"2001","journal-title":"Respir. Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1093\/humrep\/der377","article-title":"CFTR mutations in men with congenital bilateral absence of the vas deferens (CBAVD): A systemic review and meta-analysis","volume":"27","author":"Yu","year":"2012","journal-title":"Hum. Reprod."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1056\/NEJM199506013322204","article-title":"Mutations in the cystic fibrosis gene in patients with congenital absence of the vas deferens","volume":"332","author":"Casals","year":"1995","journal-title":"N. Engl. J. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1101\/cshperspect.a009548","article-title":"The influence of genetics on cystic fibrosis phenotypes","volume":"2","author":"Knowles","year":"2012","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1016\/S2213-2600(16)00023-0","article-title":"Progress in therapies for cystic fibrosis","volume":"4","author":"Amaral","year":"2016","journal-title":"Lancet Respir. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1164\/rccm.200608-1164OC","article-title":"Heritability of lung disease severity in cystic fibrosis","volume":"175","author":"Vanscoy","year":"2007","journal-title":"Am. J. Respi.r Crit. Care Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1111\/j.1365-2605.2004.00485.x","article-title":"CFTR mutations and polymorphisms in male infertility","volume":"27","author":"Cuppens","year":"2004","journal-title":"Int. J. Androl."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1093\/molehr\/8.8.758","article-title":"Expression of cystic fibrosis transmembrane conductance regulator during early human embryo development","volume":"8","year":"2002","journal-title":"Mol. Hum. Reprod."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1038\/cr.2012.88","article-title":"CFTR mediates bicarbonate-dependent activation of miR-125b in preimplantation embryo development","volume":"22","author":"Lu","year":"2012","journal-title":"Cell Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1744","DOI":"10.1093\/humrep\/deq094","article-title":"Involvement of CFTR in oviductal HCO-3 secretion and its effect on soluble adenylate cyclase-dependent early embryo development","volume":"25","author":"Chen","year":"2010","journal-title":"Hum. Reprod."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"28402","DOI":"10.1038\/srep28402","article-title":"Involvement of Cl\u2212\/HCO3\u2212 exchanger SLC26A3 and SLC26A6 in preimplantation embryo cleavage","volume":"6","author":"Lu","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1038\/nature15729","article-title":"\u0394f508 CFTR interactome remodelling promotes rescue of cystic fibrosis","volume":"528","author":"Pankow","year":"2015","journal-title":"Nature"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.bbamcr.2018.01.005","article-title":"Retinoic acid promotes stem cell differentiation and embryonic development by transcriptionally activating CFTR","volume":"1865","author":"Li","year":"2018","journal-title":"Biochim. Biophys. Acta - Mol. Cell Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1530\/REP-17-0681","article-title":"CFTR is required for the migration of primordial germ cells during zebrafish early embryogenesis","volume":"156","author":"Liao","year":"2018","journal-title":"Reproduction"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1242\/dev.024166","article-title":"Mechanical control of tissue and organ development","volume":"137","author":"Mammoto","year":"2010","journal-title":"Development"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.devcel.2014.06.012","article-title":"Parasympathetic Innervation Regulates Tubulogenesis in the Developing Salivary Gland","volume":"30","author":"Nedvetsky","year":"2014","journal-title":"Dev. Cell"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.gde.2015.01.010","article-title":"Developing pressures: Fluid forces driving morphogenesis","volume":"32","author":"Navis","year":"2015","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2750","DOI":"10.1242\/dev.104794","article-title":"Cellular and physical mechanisms of branching morphogenesis","volume":"141","author":"Varner","year":"2014","journal-title":"Development"},{"key":"ref_76","first-page":"4328","article-title":"Microfluidic chest cavities reveal that transmural pressure controls the rate of lung development","volume":"144","author":"Nelson","year":"2017","journal-title":"Development"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1002\/dvdy.20237","article-title":"Control of basement membrane remodeling and epithelial branching morphogenesis in embryonic lung by Rho and cytoskeletal tension","volume":"232","author":"Moore","year":"2005","journal-title":"Dev. Dyn."},{"key":"ref_78","first-page":"4396","article-title":"CFTR interacts with ZO-1 to regulate tight junction assembly and epithelial differentiation through the ZONAB pathway","volume":"127","author":"Ruan","year":"2014","journal-title":"J. Cell Sci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1242\/bio.014076","article-title":"The zebrafish Kupffer\u2019s vesicle as a model system for the molecular mechanisms by which the lack of Polycystin-2 leads to stimulation of CFTR","volume":"4","author":"Jacinto","year":"2015","journal-title":"Biol. Open"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1840","DOI":"10.1016\/j.cub.2010.09.012","article-title":"Cse1l is a negative regulator of CFTR-dependent fluid secretion","volume":"20","author":"Bagnat","year":"2010","journal-title":"Curr. Biol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-213X-8-70","article-title":"CFTR and Wnt\/beta-catenin signaling in lung development","volume":"8","author":"Cohen","year":"2008","journal-title":"BMC Dev. Biol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.ydbio.2014.12.034","article-title":"Loss of cftr function leads to pancreatic destruction in larval zebrafish","volume":"399","author":"Navis","year":"2015","journal-title":"Dev. Biol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"L472","DOI":"10.1152\/ajplung.1992.262.4.L472","article-title":"Expression of CFTR and presence of cAMP-mediated fluid secretion in human fetal lung","volume":"262","author":"McCray","year":"1992","journal-title":"Am. J. Physiol. Cell Mol. Physiol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/978-1-4684-5934-0_24","article-title":"Regulation of expression of CFTR in human intestinal epithelial cells","volume":"290","author":"Buchwald","year":"1991","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"4495","DOI":"10.1016\/S0021-9258(20)64350-2","article-title":"Cellular differentiation regulates expression of Cl- transport and cystic fibrosis transmembrane conductance regulator mRNA in human intestinal cells","volume":"266","author":"Guggino","year":"1991","journal-title":"J. Biol. Chem."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2487","DOI":"10.1002\/j.1460-2075.1992.tb05313.x","article-title":"Regulation of CFTR expression and function during differentiation of intestinal epithelial cells","volume":"11","author":"Sood","year":"1992","journal-title":"EMBO J."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"19299","DOI":"10.1016\/S0021-9258(18)41774-7","article-title":"Regulation of cystic fibrosis transmembrane conductance regulator (CFTR) gene transcription and alternative RNA splicing in a model of developing intestinal epithelium","volume":"267","author":"Blackmon","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/S0171-9335(98)80037-X","article-title":"Targeting of CFTR protein is linked to the polarization of human pancreatic duct cells in culture","volume":"76","author":"Hollande","year":"1998","journal-title":"Eur. J. Cell Biol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1172\/JCI5731","article-title":"DeltaF508 CFTR protein expression in tissues from patients with cystic fibrosis","volume":"103","author":"Claass","year":"1999","journal-title":"J. Clin. Invest."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1038\/labinvest.3780090","article-title":"Cystic fibrosis F508del patients have apically localized CFTR in a reduced number of airway cells","volume":"80","author":"Penque","year":"2000","journal-title":"Lab. Invest."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1016\/S0046-8177(97)90010-1","article-title":"Decreased expression of the cystic fibrosis transmembrane conductance regulator protein in remodeled airway epithelium from lung transplanted patients","volume":"28","author":"Hamm","year":"1997","journal-title":"Hum. Pathol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"C599","DOI":"10.1152\/ajpcell.1998.275.2.C599","article-title":"Activation of DeltaF508 CFTR in an epithelial monolayer","volume":"275","author":"Venglarik","year":"1998","journal-title":"Am. J. Physiol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1021\/cb300484r","article-title":"HGF stimulation of Rac1 signaling enhances pharmacological correction of the most prevalent cystic fibrosis mutant F508del-CFTR","volume":"8","author":"Moniz","year":"2013","journal-title":"ACS Chem. Biol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/S0024-3205(00)00985-1","article-title":"Changes in expression of ion channels and aquaporins mRNA during differentiation in normal human nasal epithelial cells","volume":"68","author":"Jun","year":"2001","journal-title":"Life Sci."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1465-9921-14-38","article-title":"Changes in transcriptome of native nasal epithelium expressing F508del-CFTR and intersecting data from comparable studies","volume":"14","author":"Clarke","year":"2013","journal-title":"Respir. Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"121424","DOI":"10.1155\/2012\/121424","article-title":"The Plasma Membrane Potential and the Organization of the Actin Cytoskeleton of Epithelial Cells","volume":"2012","author":"Chifflet","year":"2012","journal-title":"Int. J. Cell Biol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1016\/j.bbamem.2007.07.012","article-title":"Adherens and tight junctions: Structure, function and connections to the actin cytoskeleton","volume":"1778","author":"Hartsock","year":"2008","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1002\/cm.20404","article-title":"Connexins, cell motility, and the cytoskeleton","volume":"66","author":"Olk","year":"2009","journal-title":"Cell Motil. Cytoskeleton"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"C1552","DOI":"10.1152\/ajpcell.1995.268.6.C1552","article-title":"cAMP-independent regulation of CFTR by the actin cytoskeleton","volume":"268","author":"Prat","year":"1995","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"C1160","DOI":"10.1152\/ajpcell.1999.277.6.C1160","article-title":"Actin filament organization is required for proper cAMP-dependent activation of CFTR","volume":"277","author":"Prat","year":"1999","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1007\/s00249-001-0188-9","article-title":"Evidence for direct interaction between actin and the cystic fibrosis transmembrane conductance regulator","volume":"30","author":"Chasan","year":"2002","journal-title":"Eur. Biophys. J."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Stanke, F., Hedtfeld, S., Becker, T., and T\u00fcmmler, B. (2011). An association study on contrasting cystic fibrosis endophenotypes recognizes KRT8 but not KRT18 as a modifier of cystic fibrosis disease severity and CFTR mediated residual chloride secretion. BMC Med. Genet., 12.","DOI":"10.1186\/1471-2350-12-62"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1091\/mbc.e09-03-0185","article-title":"Na+\/H+ exchanger regulatory factor 1 overexpression-dependent increase of cytoskeleton organization is fundamental in the rescue of F508del cystic fibrosis transmembrane conductance regulator in human airway CFBE41o- cells","volume":"21","author":"Favia","year":"2010","journal-title":"Mol. Biol. Cell"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.yexmp.2009.09.018","article-title":"CFTR and tight junctions in cultured bronchial epithelial cells","volume":"88","author":"Nilsson","year":"2010","journal-title":"Exp. Mol. Pathol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.yexcr.2016.08.025","article-title":"Human airway epithelial cells investigated by atomic force microscopy: A hint to cystic fibrosis epithelial pathology","volume":"348","author":"Lasalvia","year":"2016","journal-title":"Exp. Cell Res."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1242\/jcs.089086","article-title":"CFTR regulation in human airway epithelial cells requires integrity of the actin cytoskeleton and compartmentalized cAMP and PKA activity","volume":"125","author":"Monterisi","year":"2012","journal-title":"J. Cell Sci."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1093\/emboj\/16.1.35","article-title":"Ezrin is a cyclic AMP-dependent protein kinase anchoring protein","volume":"16","author":"Dransfield","year":"1997","journal-title":"EMBO J."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"19797","DOI":"10.1074\/jbc.273.31.19797","article-title":"An apical PDZ protein anchors the cystic fibrosis transmembrane conductance regulator to the cytoskeleton","volume":"273","author":"Short","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"40925","DOI":"10.1074\/jbc.M505103200","article-title":"Na+\/H+ exchanger regulatory factor isoform 1 overexpression modulates cystic fibrosis transmembrane conductance regulator (CFTR) expression and activity in human airway 16HBE14o- cells and rescues DeltaF508 CFTR functional expression in cystic fibrosis c","volume":"280","author":"Guerra","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1038\/labinvest.2012.123","article-title":"NHERF1 and CFTR restore tight junction organisation and function in cystic fibrosis airway epithelial cells: Role of ezrin and the RhoA\/ROCK pathway","volume":"92","author":"Castellani","year":"2012","journal-title":"Lab. Investig."},{"key":"ref_111","first-page":"G275","article-title":"Barrier function of epithelia","volume":"241","author":"Powell","year":"1981","journal-title":"Am. J. Physiol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1159\/000331742","article-title":"Paracellular permeability of bronchial epithelium is controlled by CFTR","volume":"28","author":"Weiser","year":"2011","journal-title":"Cell Physiol. Biochem."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"L475","DOI":"10.1152\/ajplung.00060.2015","article-title":"Junctional abnormalities in human airway epithelial cells expressing F508del CFTR","volume":"309","author":"Molina","year":"2015","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"3","DOI":"10.4103\/1008-682X.165946","article-title":"Regulation of epithelial function, differentiation, and remodeling in the epididymis","volume":"18","author":"Breton","year":"2016","journal-title":"Asian J. Androl."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1083\/jcb.147.6.1351","article-title":"Direct binding of three tight junction-associated MAGUKs, ZO-1, ZO-2, and ZO-3, with the COOH termini of claudins","volume":"147","author":"Itoh","year":"1999","journal-title":"J. Cell Biol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/s00441-013-1734-3","article-title":"Disrupted tight junctions in the small intestine of cystic fibrosis mice","volume":"355","year":"2014","journal-title":"Cell Tissue Res."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"S81","DOI":"10.1007\/s004240100650","article-title":"Regulation of gap junctional communication in CFTR-expressing pancreatic epithelial cells","volume":"443","author":"Chanson","year":"2001","journal-title":"Pflugers Arch."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"S42","DOI":"10.1016\/j.jcf.2019.09.010","article-title":"Regeneration of airway epithelial cells to study rare cell states in cystic fibrosis","volume":"19","author":"Barbry","year":"2020","journal-title":"J. Cyst Fibros"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"L715","DOI":"10.1152\/ajplung.00361.2009","article-title":"Epithelial repair mechanisms in the lung","volume":"298","author":"Crosby","year":"2010","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1172\/JCI45961","article-title":"The three R\u2019s of lung health and disease: Repair, remodeling, and regeneration","volume":"121","author":"Beers","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"C55","DOI":"10.1152\/ajpcell.1992.263.1.C55","article-title":"Expression and regulation of the cystic fibrosis gene during rat liver regeneration","volume":"263","author":"Davin","year":"1992","journal-title":"Am. J. Physiol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1097\/01.LAB.0000022221.88025.43","article-title":"Polarized expression of cystic fibrosis transmembrane conductance regulator and associated epithelial proteins during the regeneration of human airway surface epithelium in three-dimensional culture","volume":"82","author":"Castillon","year":"2002","journal-title":"Lab. Investig."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1007\/BF00463582","article-title":"The preservation and regeneration of cilia on human nasal epithelial cells cultured in vitro","volume":"246","author":"Jorissen","year":"1989","journal-title":"Arch. Otorhinolaryngol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1002\/jgm.570","article-title":"Regeneration of a well-differentiated human airway surface epithelium by spheroid and lentivirus vector-transduced airway cells","volume":"6","author":"Castillon","year":"2004","journal-title":"J. Gene Med."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1165\/ajrcmb.12.6.7766425","article-title":"Cell proliferation in bronchial epithelium and submucosal glands of cystic fibrosis patients","volume":"12","author":"Leigh","year":"1995","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1164\/rccm.200410-1398OC","article-title":"Basal-like Cells Constitute the Proliferating Cell Population in Cystic Fibrosis Airways","volume":"172","author":"Voynow","year":"2005","journal-title":"Am. J. Respir Crit. Care Med."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.biocel.2014.02.010","article-title":"Cx26 regulates proliferation of repairing basal airway epithelial cells","volume":"52","author":"Crespin","year":"2014","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1002\/path.4471","article-title":"Cystic fibrosis airway epithelium remodelling: Involvement of inflammation","volume":"235","author":"Adam","year":"2015","journal-title":"J. Pathol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/j.jcf.2018.03.010","article-title":"CFTR rescue with VX-809 and VX-770 favors the repair of primary airway epithelial cell cultures from patients with class II mutations in the presence of Pseudomonas aeruginosa exoproducts","volume":"17","author":"Adam","year":"2018","journal-title":"J. Cyst. Fibros."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1051\/medsci\/200521121063","article-title":"[Repair and regeneration of the airway epithelium]","volume":"21","author":"Coraux","year":"2005","journal-title":"Med. Sci. (Paris)"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"L394","DOI":"10.1152\/ajplung.00091.2012","article-title":"Increased expression of senescence markers in cystic fibrosis airways","volume":"304","author":"Fischer","year":"2013","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1038\/s41597-019-0256-6","article-title":"Transcriptomic profile of cystic fibrosis airway epithelial cells undergoing repair","volume":"6","author":"Zoso","year":"2019","journal-title":"Sci. Data"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1515\/bnm-2016-0002","article-title":"In vitro wound healing assays \u2013 state of the art","volume":"17","author":"Stamm","year":"2016","journal-title":"BioNanoMaterials"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"L945","DOI":"10.1152\/ajplung.00149.2011","article-title":"Regulation of normal and cystic fibrosis airway epithelial repair processes by TNF-\u03b1 after injury","volume":"301","author":"Trinh","year":"2011","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"C888","DOI":"10.1152\/ajpcell.00313.2010","article-title":"CFTR channels and wound healing. Focus on \u2018Cystic fibrosis transmembrane conductance regulator is involved in airway epithelial wound repair\u2019","volume":"299","author":"Kirk","year":"2010","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1183\/09031936.00221711","article-title":"Improvement of defective cystic fibrosis airway epithelial wound repair after CFTR rescue","volume":"40","author":"Trinh","year":"2012","journal-title":"Eur. Respir. J."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"C819","DOI":"10.1152\/ajpcell.00168.2013","article-title":"Reduced GM1 ganglioside in CFTR-deficient human airway cells results in decreased \u03b21-integrin signaling and delayed wound repair","volume":"306","author":"Itokazu","year":"2014","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.placenta.2013.12.004","article-title":"Cystic fibrosis transmembrane regulator (CFTR) in human trophoblast BeWo cells and its relation to cell migration","volume":"35","author":"Marino","year":"2014","journal-title":"Placenta"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.1002\/jcp.24931","article-title":"Dynamically Regulated CFTR Expression and Its Functional Role in Cutaneous Wound Healing","volume":"230","author":"Dong","year":"2015","journal-title":"J. Cell Physiol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"e100621","DOI":"10.1371\/journal.pone.0100621","article-title":"Paracellular transport through healthy and cystic fibrosis bronchial epithelial cell lines--do we have a proper model?","volume":"9","author":"Molenda","year":"2014","journal-title":"PLoS ONE"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1183\/09031936.00099506","article-title":"Cystic fibrosis mortality and survival in the UK: 1947-2003","volume":"29","author":"Dodge","year":"2007","journal-title":"Eur. Respir. J."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1203\/00006450-196909000-00001","article-title":"Childhood Cancer and Congenital Defects A Study of U.S. Death Certificates During the Period 1960\u20131966","volume":"3","author":"Miller","year":"1969","journal-title":"Pediatr. Res."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1016\/0016-5085(82)90323-7","article-title":"Carcinoma of extrahepatic biliary system in an adult with cystic fibrosis","volume":"82","author":"King","year":"1982","journal-title":"Gastroenterology"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1136\/thx.40.3.199","article-title":"Adenocarcinoma in cystic fibrosis","volume":"40","author":"Davis","year":"1985","journal-title":"Thorax"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1016\/S0002-9343(88)80116-5","article-title":"Pancreatic adenocarcinoma in a patient with cystic fibrosis","volume":"85","author":"McIntosh","year":"1988","journal-title":"Am. J. Med."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1016\/S0140-6736(87)91598-4","article-title":"Cystic Fibrosis and Ileal Carcinoma","volume":"330","author":"Siraganian","year":"1987","journal-title":"Lancet"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1177\/003693308603100210","article-title":"Bowel Adenocarcinoma in a Patient with Cystic Fibrosis","volume":"31","author":"Roberts","year":"1986","journal-title":"Scott. Med. J."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"2441","DOI":"10.1002\/1097-0142(19860615)57:12<2441::AID-CNCR2820571232>3.0.CO;2-W","article-title":"Cystic fibrosis complicated by acute leukemia","volume":"57","author":"Biggs","year":"1986","journal-title":"Cancer"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1016\/S0022-3476(05)80296-3","article-title":"Cancer risk among patients with cystic fibrosis","volume":"119","author":"Neglia","year":"1991","journal-title":"J. Pediatr."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1038\/bjc.1993.474","article-title":"A cohort study of cystic fibrosis and malignancy","volume":"68","author":"Sheldon","year":"1993","journal-title":"Br. J. Cancer"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1053\/j.gastro.2017.12.012","article-title":"Cystic Fibrosis Colorectal Cancer Screening Consensus Recommendations","volume":"154","author":"Hadjiliadis","year":"2018","journal-title":"Gastroenterology"},{"key":"ref_152","first-page":"1","article-title":"Lung cancer in a CF patient: Combination of bad luck or is there more to say?","volume":"00","author":"Vekens","year":"2020","journal-title":"Acta Clin. Belg."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1136\/bmj.302.6779.760","article-title":"Frequency of carriers of cystic fibrosis gene among patients with myeloid malignancy and melanoma","volume":"302","author":"Warren","year":"1991","journal-title":"BMJ"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1002\/(SICI)1098-1004(1997)10:1<45::AID-HUMU6>3.0.CO;2-L","article-title":"The cystic fibrosis \u0394F508 gene mutation and cancer","volume":"10","author":"Padua","year":"1997","journal-title":"Hum. Mutat."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.lungcan.2010.01.005","article-title":"Cystic fibrosis transmembrane conductance regulator gene mutation and lung cancer risk","volume":"70","author":"Li","year":"2010","journal-title":"Lung Cancer"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.jcf.2007.07.011","article-title":"Cystic fibrosis transmembrane conductance regulator (CFTR) gene 5T allele may protect against prostate cancer: A case-control study in Chinese Han population","volume":"7","author":"Qiao","year":"2008","journal-title":"J. Cyst. Fibros"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1136\/gut.2005.074534","article-title":"Cystic fibrosis transmembrane regulator gene carrier status is a risk factor for young onset pancreatic adenocarcinoma","volume":"54","author":"McWilliams","year":"2005","journal-title":"Gut"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1002\/cncr.24697","article-title":"Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations and risk for pancreatic adenocarcinoma","volume":"116","author":"McWilliams","year":"2010","journal-title":"Cancer"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1002\/(SICI)1097-0215(19981023)79:5<487::AID-IJC7>3.0.CO;2-X","article-title":"CFTR \u0394F508 carrier status, risk of breast cancer before the age of 40 and histological grading in a population-based case-control study","volume":"79","author":"Southey","year":"1998","journal-title":"Int. J. Cancer"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"2953","DOI":"10.1002\/ijc.24679","article-title":"Cancer risk among patients with cystic fibrosis and their first-degree relatives","volume":"125","author":"Johannesson","year":"2009","journal-title":"Int J. Cancer"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1038\/nm0596-593","article-title":"Cystic fibrosis hetero-and homozygosity is associated with inhibition of breast cancer growth","volume":"2","author":"Abraham","year":"1996","journal-title":"Nat. Med."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1002\/ijc.24394","article-title":"Methylation of multiple genes as molecular markers for diagnosis of a small, well-differentiated hepatocellular carcinoma","volume":"125","author":"Moribe","year":"2009","journal-title":"Int J. Cancer"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"7296","DOI":"10.1158\/1078-0432.CCR-07-0861","article-title":"A novel set of DNA methylation markers in urine sediments for sensitive\/specific detection of bladder cancer","volume":"13","author":"Yu","year":"2007","journal-title":"Clin. Cancer Res."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1002\/pros.22833","article-title":"A DNA hypermethylation profile reveals new potential biomarkers for prostate cancer diagnosis and prognosis","volume":"74","author":"Ashour","year":"2014","journal-title":"Prostate"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1002\/cbin.11260","article-title":"Promoter hypermethylation of the CFTR gene as a novel diagnostic and prognostic marker of breast cancer","volume":"44","author":"Liu","year":"2020","journal-title":"Cell Biol. Int."},{"key":"ref_166","doi-asserted-by":"crossref","unstructured":"Shin, Y., Kim, M., Won, J., Kim, J., Oh, S.B., Lee, J.-H., and Park, K. (2020). Epigenetic Modification of CFTR in Head and Neck Cancer. J. Clin. Med., 9.","DOI":"10.3390\/jcm9030734"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"2408","DOI":"10.18632\/aging.102751","article-title":"Integrated analysis of DNA methylation and mRNA expression profiles to identify key genes involved in the regrowth of clinically non-functioning pituitary adenoma","volume":"12","author":"Cheng","year":"2020","journal-title":"Aging (Albany NY)"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/sj.onc.1209764","article-title":"MUC4 expression is regulated by cystic fibrosis transmembrane conductance regulator in pancreatic adenocarcinoma cells via transcriptional and post-translational mechanisms","volume":"26","author":"Singh","year":"2007","journal-title":"Oncogene"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"2107","DOI":"10.3892\/ijo.2015.2921","article-title":"The cystic fibrosis transmembrane conductance regulator as a biomarker in non-small cell lung cancer","volume":"46","author":"Li","year":"2015","journal-title":"Int J. Oncol."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"42","DOI":"10.21037\/jtd.2017.01.04","article-title":"Weighted gene co-expression network analysis in identification of metastasis-related genes of lung squamous cell carcinoma based on the Cancer Genome Atlas database","volume":"9","author":"Tian","year":"2017","journal-title":"J. Thorac Dis"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.1002\/cbin.11069","article-title":"CFTR inhibits the invasion and growth of esophageal cancer cells by inhibiting the expression of NF-\u03baB","volume":"42","author":"Li","year":"2018","journal-title":"Cell Biol. Int."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"4191","DOI":"10.1038\/onc.2015.483","article-title":"CFTR is a tumor suppressor gene in murine and human intestinal cancer","volume":"35","author":"Than","year":"2016","journal-title":"Oncogene"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1016\/j.bbrc.2018.12.080","article-title":"CFTR activation suppresses glioblastoma cell proliferation, migration and invasion","volume":"508","author":"Zhong","year":"2019","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"2282","DOI":"10.1038\/onc.2012.251","article-title":"CFTR suppresses tumor progression through miR-193b targeting urokinase plasminogen activator (uPA) in prostate cancer","volume":"32","author":"Xie","year":"2013","journal-title":"Oncogene"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/j.ygyno.2012.02.015","article-title":"Overexpression of cystic fibrosis transmembrane conductance regulator (CFTR) is associated with human cervical cancer malignancy, progression and prognosis","volume":"125","author":"Peng","year":"2012","journal-title":"Gynecol. Oncol."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1097\/IGC.0b013e318292da82","article-title":"Constitutive Activation of Nuclear Factor \u03baB Contributes to Cystic Fibrosis Transmembrane Conductance Regulator Expression and Promotes Human Cervical Cancer Progression and Poor Prognosis","volume":"23","author":"Wu","year":"2013","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"2227","DOI":"10.3892\/or.2015.3829","article-title":"High level of CFTR expression is associated with tumor aggression and knockdown of CFTR suppresses proliferation of ovarian cancer in vitro and in vivo","volume":"33","author":"Xu","year":"2015","journal-title":"Oncol. Rep."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1210\/endo.133.2.7688293","article-title":"Stimulation of the cystic fibrosis transmembrane regulator expression by estrogen in vivo","volume":"133","author":"Rochwerger","year":"1993","journal-title":"Endocrinology"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/j.bbrc.2007.02.166","article-title":"Intrinsic pro-angiogenic status of cystic fibrosis airway epithelial cells","volume":"356","author":"Verhaeghe","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.cell.2009.11.007","article-title":"Epithelial-Mesenchymal Transitions in Development and Disease","volume":"139","author":"Thiery","year":"2009","journal-title":"Cell"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1038\/nrm3758","article-title":"Molecular mechanisms of epithelial-mesenchymal transition","volume":"15","author":"Lamouille","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1172\/JCI39104","article-title":"The basics of epithelial-mesenchymal transition","volume":"119","author":"Kalluri","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_183","doi-asserted-by":"crossref","unstructured":"Snodgrass, S.M., Cihil, K.M., Cornuet, P.K., Myerburg, M.M., and Swiatecka-Urban, A. (2013). Tgf-\u03b21 Inhibits Cftr Biogenesis and Prevents Functional Rescue of \u0394F508-Cftr in Primary Differentiated Human Bronchial Epithelial Cells. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0063167"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"81","DOI":"10.7555\/JBR.31.20160124","article-title":"Re-evaluating the role of epithelial-mesenchymal-transition in cancer progression","volume":"32","author":"Sulaiman","year":"2018","journal-title":"J. Biomed. Res."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1038\/ng.2609","article-title":"Genome-wide association study identifies multiple susceptibility loci for pulmonary fibrosis","volume":"45","author":"Fingerlin","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1097\/MCP.0000000000000476","article-title":"Trade-offs in aging lung diseases","volume":"24","year":"2018","journal-title":"Curr. Opin. Pulm. Med."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.jcf.2017.11.003","article-title":"FAM13A is a modifier gene of cystic fibrosis lung phenotype regulating rhoa activity, actin cytoskeleton dynamics and epithelial-mesenchymal transition","volume":"17","author":"Corvol","year":"2018","journal-title":"J. Cyst. Fibros."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1002\/dvdy.24541","article-title":"Epithelial-mesenchymal transition, a spectrum of states: Role in lung development, homeostasis, and disease","volume":"247","author":"Jolly","year":"2018","journal-title":"Dev. Dyn."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1002\/ppul.21430","article-title":"Plasma TGF-\u03b21 in pediatric cystic fibrosis: Potential biomarker of lung disease and response to therapy","volume":"46","author":"Harris","year":"2011","journal-title":"Pediatr. Pulmonol."},{"key":"ref_190","first-page":"1","article-title":"Defective CFTR leads to aberrant \u03b2-catenin activation and kidney fibrosis","volume":"7","author":"Zhang","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.bbrc.2019.01.100","article-title":"CFTR constrains the differentiation from mouse embryonic stem cells to intestine lineage cells","volume":"510","author":"Li","year":"2019","journal-title":"Biochem. Biophys. Res. Commun."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/9\/3133\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T14:09:24Z","timestamp":1760364564000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/9\/3133"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,29]]},"references-count":191,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2020,5]]}},"alternative-id":["ijms21093133"],"URL":"https:\/\/doi.org\/10.3390\/ijms21093133","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,29]]}}}