{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T04:36:49Z","timestamp":1789965409164,"version":"4.0.1"},"reference-count":93,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2018,7,17]],"date-time":"2018-07-17T00:00:00Z","timestamp":1531785600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The acquisition of invasive properties preceding tumor metastasis is critical for cancer progression. This phenomenon may result from mutagenic disruption of typical cell function, but recent evidence suggests that cancer cells frequently co-opt normal developmental programs to facilitate invasion as well. The signaling cascades that have been implicated present an obstacle to identifying effective therapeutic targets because of their complex nature and modulatory capacity through crosstalk with other pathways. Substantial efforts have been made to study invasive behavior during organogenesis in several organisms, but another model found in Drosophilamelanogaster has not been thoroughly explored. The air sac primordium (ASP) appears to be a suitable candidate for investigating the genes and morphogens required for invasion due to the distinct overlap in the events that occur during its normal growth and the development of metastatic tumor cells. Among these events are the conversion of larval cells in the trachea into a population of mitotically active cells, reduced cell\u2013cell contact along the leading edge of the ASP, and remodeling of the extracellular matrix (ECM) that surrounds the structure. Here, we summarize the development of ASPs and invasive behavior observed therein.<\/jats:p>","DOI":"10.3390\/ijms19072074","type":"journal-article","created":{"date-parts":[[2018,7,18]],"date-time":"2018-07-18T08:45:42Z","timestamp":1531903542000},"page":"2074","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The Air Sac Primordium of Drosophila: A Model for Invasive Development"],"prefix":"10.3390","volume":"19","author":[{"given":"Nathan","family":"Powers","sequence":"first","affiliation":[{"name":"Department of Biology and Biotechnology Center, Western Kentucky University, 1906 College Heights Boulevard, TCCW 351, Bowling Green, KY 42101, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajay","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnology Center, Western Kentucky University, 1906 College Heights Boulevard, TCCW 351, Bowling Green, KY 42101, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,7,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.3389\/fimmu.2017.01625","article-title":"Hypoxic Stress-Induced Tumor and Immune Plasticity, Suppression, and Impact on Tumor Heterogeneity","volume":"8","author":"Terry","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: The next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2721","DOI":"10.1073\/pnas.0611666104","article-title":"Basement membrane remodeling is essential for Drosophila disc eversion and tumor invasion","volume":"104","author":"Srivastava","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0925-4773(01)00615-3","article-title":"The JAK\/STAT pathway is required for border cell migration during Drosophila oogenesis","volume":"111","author":"Beccari","year":"2002","journal-title":"Mech. Dev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.3892\/ijo.2015.3160","article-title":"The JAK\/STAT signaling cascade in gastric carcinoma (Review)","volume":"47","author":"Khanna","year":"2015","journal-title":"Int. J. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.tibs.2007.12.002","article-title":"Mining for JAK-STAT mutations in cancer","volume":"33","author":"Constantinescu","year":"2008","journal-title":"Trends Biochem. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.semcdb.2014.03.023","article-title":"JAK\/STAT pathway dysregulation in tumors: A Drosophila perspective","volume":"28","author":"Amoyel","year":"2014","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1002\/cbf.3120","article-title":"Platelet-derived growth factor (PDGF) signalling in cancer: Rapidly emerging signalling landscape","volume":"33","author":"Farooqi","year":"2015","journal-title":"Cell Biochem. Funct."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1007\/s00280-013-2298-3","article-title":"The VEGF pathway in lung cancer","volume":"72","author":"Alevizakos","year":"2013","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_10","first-page":"199","article-title":"VEGF expression in pancreatic cancer and other malignancies: A review of the literature","volume":"53","author":"Costache","year":"2015","journal-title":"Rom. J. Intern. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1517\/14728222.2011.648617","article-title":"Targeting the EGFR signaling pathway in cancer therapy","volume":"16","author":"Seshacharyulu","year":"2012","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.ydbio.2009.11.014","article-title":"Cell migration during morphogenesis","volume":"341","author":"Aman","year":"2010","journal-title":"Dev. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1083\/jcb.201010003","article-title":"Cell behaviors regulated by guidance cues in collective migration of border cells","volume":"192","author":"Poukkula","year":"2011","journal-title":"J. Cell Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S0092-8674(00)81683-9","article-title":"The hallmarks of cancer","volume":"100","author":"Hanahan","year":"2000","journal-title":"Cell"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1923","DOI":"10.1158\/1078-0432.CCR-07-5259","article-title":"Comparisons of metastases in different organs: Biological and clinical implications","volume":"14","author":"Tarin","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1126\/science.1203543","article-title":"A perspective on cancer cell metastasis","volume":"331","author":"Chaffer","year":"2011","journal-title":"Science"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1002\/dvdy.22771","article-title":"Drosophila cancer models","volume":"241","author":"Rudrapatna","year":"2012","journal-title":"Dev. Dyn."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4027","DOI":"10.1242\/jcs.02522","article-title":"Transition from non-motile behaviour to directed migration during early PGC development in zebrafish","volume":"118","author":"Blaser","year":"2005","journal-title":"J. Cell Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.ydbio.2012.05.017","article-title":"Drosophila apc regulates delamination of invasive epithelial clusters","volume":"368","author":"Ghiglione","year":"2012","journal-title":"Dev. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1159\/000348418","article-title":"The neural crest and cancer: A developmental spin on melanoma","volume":"198","author":"Kulesa","year":"2013","journal-title":"Cells Tissues Organs"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1242\/dmm.018689","article-title":"Phenotype-driven chemical screening in zebrafish for compounds that inhibit collective cell migration identifies multiple pathways potentially involved in metastatic invasion","volume":"8","author":"Gallardo","year":"2015","journal-title":"Dis. Model. Mech."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/S1534-5807(02)00202-2","article-title":"FGF is an essential mitogen and chemoattractant for the air sacs of the Drosophila tracheal system","volume":"3","author":"Sato","year":"2002","journal-title":"Dev. Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/j.devcel.2005.10.008","article-title":"Distinct roles for two receptor tyrosine kinases in epithelial branching morphogenesis in Drosophila","volume":"9","author":"Cabernard","year":"2005","journal-title":"Dev. Cell"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.ydbio.2008.03.025","article-title":"Larval cells become imaginal cells under the control of homothorax prior to metamorphosis in the Drosophila tracheal system","volume":"318","author":"Sato","year":"2008","journal-title":"Dev. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3090","DOI":"10.1016\/j.febslet.2015.08.036","article-title":"A Cathepsin-L is required for invasive behavior during Air Sac Primordium development in Drosophila melanogaster","volume":"589","author":"Dong","year":"2015","journal-title":"FEBS Lett."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.ydbio.2009.09.005","article-title":"Regulation of Drosophila matrix metalloprotease Mmp2 is essential for wing imaginal disc:trachea association and air sac tubulogenesis","volume":"335","author":"Guha","year":"2009","journal-title":"Dev. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.devcel.2009.11.004","article-title":"Spatial Restriction of FGF Signaling by a Matrix Metalloprotease Controls Branching Morphogenesis","volume":"18","author":"Wang","year":"2010","journal-title":"Dev. Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/0012-1606(92)90052-I","article-title":"What are and what are not imaginal discs: Reevaluation of some basic concepts (insecta, holometabola)","volume":"154","year":"1992","journal-title":"Dev. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1007\/s00427-004-0458-5","article-title":"Development of the adult leg epidermis in Manduca sexta: Contribution of different larval cell populations","volume":"215","author":"Tanaka","year":"2005","journal-title":"Dev. Genes Evol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.ydbio.2005.09.005","article-title":"Tracheal branch repopulation precedes induction of the Drosophila dorsal air sac primordium","volume":"287","author":"Guha","year":"2005","journal-title":"Dev. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/j.celrep.2014.09.043","article-title":"Specification of differentiated adult progenitors via inhibition of endocycle entry in the Drosophila trachea","volume":"9","author":"Djabrayan","year":"2014","journal-title":"Cell Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.febslet.2013.01.054","article-title":"Engrailed homeobox transcription factors as potential markers and targets in cancer","volume":"587","author":"McGrath","year":"2013","journal-title":"FEBS Lett."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"8247","DOI":"10.3748\/wjg.v22.i37.8247","article-title":"Impact of homeobox genes in gastrointestinal cancer","volume":"22","author":"Joo","year":"2016","journal-title":"World J. Gastroenterol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3158","DOI":"10.1101\/gad.1710208","article-title":"Endocycling cells do not apoptose in response to DNA rereplication genotoxic stress","volume":"22","author":"Mehrotra","year":"2008","journal-title":"Genes Dev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1182\/blood.V96.1.259","article-title":"Overexpression of murine fizzy-related (fzr) increases natural killer cell-mediated cell death and suppresses tumor growth","volume":"96","author":"Wang","year":"2000","journal-title":"Blood"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"70481","DOI":"10.18632\/oncotarget.12026","article-title":"Identification of the APC\/C co-factor FZR1 as a novel therapeutic target for multiple myeloma","volume":"7","author":"Crawford","year":"2016","journal-title":"Oncotarget"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1958","DOI":"10.1182\/blood-2016-07-726216","article-title":"FZR1 loss increases sensitivity to DNA damage and consequently promotes murine and human B-cell acute leukemia","volume":"129","author":"Ishizawa","year":"2017","journal-title":"Blood"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1244624","DOI":"10.1126\/science.1244624","article-title":"Cytoneme-Mediated Contact-Dependent Transport of the Drosophila Decapentaplegic Signaling Protein","volume":"343","author":"Roy","year":"2014","journal-title":"Science"},{"key":"ref_39","first-page":"1458","article-title":"SERCA directs cell migration and branching across species and germ layers","volume":"6","author":"Bower","year":"2017","journal-title":"Biol. Open"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"165","DOI":"10.3390\/biom2010165","article-title":"Endoplasmic Reticulum Calcium Pumps and Cancer Cell Differentiation","volume":"2","author":"Papp","year":"2012","journal-title":"Biomolecules"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1002\/biof.142","article-title":"Endoplasmic reticulum calcium pumps and cancer","volume":"37","author":"Arbabian","year":"2011","journal-title":"BioFactors"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1016\/j.celrep.2015.12.105","article-title":"Drosophila Lung Cancer Models Identify Trametinib plus Statin as Candidate Therapeutic","volume":"14","author":"Levine","year":"2016","journal-title":"Cell Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1038\/nrm3904","article-title":"Remodelling the extracellular matrix in development and disease","volume":"15","author":"Bonnans","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_44","first-page":"741","article-title":"Prognostic value of the cysteine proteases cathepsins B and cathepsin L in human breast cancer","volume":"1","author":"Thomssen","year":"1995","journal-title":"Clin. Cancer Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/s10549-004-0714-4","article-title":"Association of cyclooxygenase-2 and matrix metalloproteinase-2 expression in human breast cancer","volume":"89","author":"Sivula","year":"2005","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.1177\/147323001003800604","article-title":"Cathepsin L is associated with proliferation and clinical outcome of urothelial carcinoma of the bladder","volume":"38","author":"Yan","year":"2010","journal-title":"J. Int. Med. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3047","DOI":"10.1007\/s13277-013-1395-6","article-title":"The MMP-1, MMP-2, and MMP-9 gene polymorphisms and susceptibility to bladder cancer: A meta-analysis","volume":"35","author":"Yan","year":"2014","journal-title":"Tumor Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1097\/IGC.0000000000000386","article-title":"The expression of tumor-derived and stromal-derived matrix metalloproteinase 2 predicted prognosis of ovarian cancer","volume":"25","author":"Fu","year":"2015","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"45995","DOI":"10.18632\/oncotarget.10276","article-title":"Overexpression of Cathepsin L is associated with chemoresistance and invasion of epithelial ovarian cancer","volume":"7","author":"Sui","year":"2016","journal-title":"Oncotarget"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1097\/01.MP.0000056984.62360.6C","article-title":"Prognostic significance of matrix metalloproteinase 2 and tissue inhibitor of metalloproteinase 2 expression in prostate cancer","volume":"16","author":"Ross","year":"2003","journal-title":"Mod. Pathol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1007\/s10585-013-9590-9","article-title":"Cathepsin L inhibition by the small molecule KGP94 suppresses tumor microenvironment enhanced metastasis associated cell functions of prostate and breast cancer cells","volume":"30","author":"Sudhan","year":"2013","journal-title":"Clin. Exp. Metastasis"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"6579","DOI":"10.1158\/1078-0432.CCR-04-0272","article-title":"Matrix Metalloproteinase-2 Status in Stromal Fibroblasts, Not in Tumor Cells, Is a Significant Prognostic Factor in Non-Small-Cell Lung Cancer","volume":"10","author":"Ishikawa","year":"2004","journal-title":"Clin. Cancer Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1007\/s12094-015-1424-6","article-title":"Overexpression of Cathepsin L is associated with gefitinib resistance in non-small cell lung cancer","volume":"18","author":"Cui","year":"2016","journal-title":"Clin. Transl. Oncol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"461","DOI":"10.3109\/07357907.2013.820318","article-title":"Prognostic significance of extracellular matrix degrading enzymes-cathepsin L and matrix metalloproteases-2 [MMP-2] in human pancreatic cancer","volume":"31","author":"Singh","year":"2013","journal-title":"Cancer Investig."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"17532","DOI":"10.3748\/wjg.v20.i46.17532","article-title":"Plasma cathepsin L: A prognostic marker for pancreatic cancer","volume":"20","author":"Singh","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"17806","DOI":"10.1038\/srep17806","article-title":"FGF coordinates air sac development by activation of the EGF ligand Vein through the transcription factor PntP2","volume":"5","author":"Cruz","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3156","DOI":"10.1101\/gad.12.20.3156","article-title":"Fgf-10 is required for both limb and lung development and exhibits striking functional similarity to Drosophila branchless","volume":"12","author":"Min","year":"1998","journal-title":"Genes Dev."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1006\/dbio.1998.8994","article-title":"FGF-10 Is a Chemotactic Factor for Distal Epithelial Buds during Lung Development","volume":"201","author":"Park","year":"1998","journal-title":"Dev. Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1002\/dvdy.22032","article-title":"Conditional gene inactivation reveals roles for Fgf10 and Fgfr2 in establishing a normal pattern of epithelial branching in the mouse lung","volume":"238","author":"Abler","year":"2008","journal-title":"Dev. Dyn."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3731","DOI":"10.1242\/dev.096560","article-title":"Localized Fgf10 expression is not required for lung branching morphogenesis but prevents differentiation of epithelial progenitors","volume":"140","author":"Volckaert","year":"2013","journal-title":"Development"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Chanut-Delalande, H., Jung, A.C., Baer, M.M., Lin, L., Payre, F., and Affolter, M. (2010). The Hrs\/Stam Complex Acts as a Positive and Negative Regulator of RTK Signaling during Drosophila Development. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0010245"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"3697","DOI":"10.1242\/dev.122.12.3697","article-title":"Cadherin-mediated cell adhesion and cell motility in Drosophila trachea regulated by the transcription factor Escargot","volume":"122","author":"Uemura","year":"1996","journal-title":"Development"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.yexcr.2017.03.044","article-title":"The Drosophila DOCK family protein Sponge is required for development of the air sac primordium","volume":"354","author":"Morishita","year":"2017","journal-title":"Exp. Cell Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"a009035","DOI":"10.1101\/cshperspect.a009035","article-title":"Effects of membrane trafficking on signaling by receptor tyrosine kinases","volume":"5","author":"Miaczynska","year":"2013","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1126\/science.1198949","article-title":"Specificity of Drosophila Cytonemes for Distinct Signaling Pathways","volume":"332","author":"Roy","year":"2011","journal-title":"Science"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e18979","DOI":"10.7554\/eLife.18979","article-title":"Cells must express components of the planar cell polarity system and extracellular matrix to support cytonemes","volume":"5","author":"Huang","year":"2016","journal-title":"eLife"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.ydbio.2007.09.015","article-title":"Drosophila glypican Dally-like acts in FGF-receiving cells to modulate FGF signaling during tracheal morphogenesis","volume":"312","author":"Yan","year":"2007","journal-title":"Dev. Biol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"17103","DOI":"10.1074\/jbc.M110.208082","article-title":"Novel contact-dependent bone morphogenetic protein (BMP) signaling mediated by heparan sulfate proteoglycans","volume":"286","author":"Dejima","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.ceb.2015.06.007","article-title":"Filopodia in cell adhesion, 3D migration and cancer cell invasion","volume":"36","author":"Jacquemet","year":"2015","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1172\/JCI67280","article-title":"Mutant p53-associated myosin-X upregulation promotes breast cancer invasion and metastasis","volume":"124","author":"Arjonen","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2118","DOI":"10.1016\/j.celrep.2015.11.012","article-title":"Specific Myosins Control Actin Organization, Cell Morphology, and Migration in Prostate Cancer Cells","volume":"13","author":"Makowska","year":"2015","journal-title":"Cell Rep."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1038\/bjc.2014.298","article-title":"Elevated expression of myosin X in tumours contributes to breast cancer aggressiveness and metastasis","volume":"111","author":"Cao","year":"2014","journal-title":"Br. J. Cancer"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1126\/science.1226929","article-title":"Dedifferentiation of neurons and astrocytes by oncogenes can induce gliomas in mice","volume":"338","author":"Bushong","year":"2012","journal-title":"Science"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.cell.2012.12.012","article-title":"Intestinal tumorigenesis initiated by dedifferentiation and acquisition of stem-cell-like properties","volume":"152","author":"Schwitalla","year":"2013","journal-title":"Cell"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"50043","DOI":"10.18632\/oncotarget.10571","article-title":"Plasticity of lung cancer stem-like cells is regulated by the transcription factor HOXA5 that is induced by oxidative stress","volume":"7","author":"Saijo","year":"2016","journal-title":"Oncotarget"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Jilkine, A., and Gutenkunst, R.N. (2014). Effect of Dedifferentiation on Time to Mutation Acquisition in Stem Cell-Driven Cancers. PLoS Comput. Biol., 10.","DOI":"10.1371\/journal.pcbi.1003481"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"9368","DOI":"10.1073\/pnas.1304889110","article-title":"Fundamental differences in endoreplication in mammals and Drosophila revealed by analysis of endocycling and endomitotic cells","volume":"110","author":"Sher","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1186\/s13046-015-0277-8","article-title":"The number of polyploid giant cancer cells and epithelial-mesenchymal transition-related proteins are associated with invasion and metastasis in human breast cancer","volume":"34","author":"Fei","year":"2015","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Lopez-S\u00e1nchez, L.M., Jimenez, C., Valverde, A., Hernandez, V., Pe\u00f1arando, J., Martinez, A., Lopez-Pedrera, C., Mu\u00f1oz-Casta\u00f1eda, J.R., De La Haba-Rodr\u00edguez, J.R., and Aranda, E. (2014). CoCl2, a mimic of hypoxia, induces formation of polyploid giant cells with stem characteristics in colon cancer. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0099143"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1007\/s00109-014-1181-y","article-title":"HOX genes and their role in the development of human cancers","volume":"92","author":"Bhatlekar","year":"2014","journal-title":"J. Mol. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1517\/14728222.2011.645805","article-title":"Targeting the Mitogen-Activated Protein Kinase RAS-RAF Signaling Pathway in Cancer Therapy","volume":"16","author":"Santarpia","year":"2012","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"33168","DOI":"10.1074\/jbc.M405102200","article-title":"Overexpression of collagenase 1 (MMP-1) is mediated by the ERK pathway in invasive melanoma cells. Role of BRAF mutation and fibroblast growth factor signaling","volume":"279","author":"Huntington","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"e08666","DOI":"10.7554\/eLife.08666","article-title":"Developmental compartments in the larval trachea of Drosophila","volume":"4","author":"Rao","year":"2015","journal-title":"eLife"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"e06114","DOI":"10.7554\/eLife.06114","article-title":"Myoblast cytonemes mediate Wg signaling from the wing imaginal disc and Delta-Notch signaling to the air sac primordium","volume":"4","author":"Huang","year":"2015","journal-title":"eLife"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1242\/dev.120.3.535","article-title":"The Serrate locus of Drosophila and its role in morphogenesis of the wing imaginal discs: Control of cell proliferation","volume":"120","author":"Speicher","year":"1994","journal-title":"Development"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Zhai, Z., Ha, N., Papagiannouli, F., Hamacher-Brady, A., Brady, N., Sorge, S., Bezdan, D., and Lohmann, I. (2012). Antagonistic regulation of apoptosis and differentiation by the cut transcription factor represents a tumor-suppressing mechanism in drosophila. PLoS Genet., 8.","DOI":"10.1371\/journal.pgen.1002582"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"4959","DOI":"10.1242\/dev.125.24.4959","article-title":"The transcription factors KNIRPS and KNIRPS RELATED control cell migration and branch morphogenesis during Drosophila tracheal development","volume":"125","author":"Chen","year":"1998","journal-title":"Development"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"10819","DOI":"10.1074\/jbc.M112.442939","article-title":"Hypoxia-inducible factor 1 (HIF-1) promotes extracellular matrix remodeling under hypoxic conditions by inducing P4HA1, P4HA2, and PLOD2 expression in fibroblasts","volume":"288","author":"Gilkes","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/j.devcel.2008.01.020","article-title":"Cell Autonomy of HIF Effects in Drosophila: Tracheal Cells Sense Hypoxia and Induce Terminal Branch Sprouting","volume":"14","author":"Centanin","year":"2008","journal-title":"Dev. Cell"},{"key":"ref_90","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_91","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1016\/j.cell.2008.09.043","article-title":"Rac Activation and Inactivation Control Plasticity of Tumor Cell Movement","volume":"135","author":"Gadea","year":"2008","journal-title":"Cell"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1016\/j.cellsig.2014.01.027","article-title":"Dock4 forms a complex with SH3YL1 and regulates cancer cell migration","volume":"26","author":"Kobayashi","year":"2014","journal-title":"Cell. Signal."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1007\/s00018-004-4472-6","article-title":"Actin polymerization machinery: The finish line of signaling networks, the starting point of cellular movement","volume":"62","author":"Disanza","year":"2005","journal-title":"Cell. Mol. Life Sci."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/7\/2074\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:12:31Z","timestamp":1760195551000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/7\/2074"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,7,17]]},"references-count":93,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2018,7]]}},"alternative-id":["ijms19072074"],"URL":"https:\/\/doi.org\/10.3390\/ijms19072074","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,7,17]]}}}