{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T19:01:01Z","timestamp":1791313261904,"version":"4.3.1"},"reference-count":56,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2019,7,8]],"date-time":"2019-07-08T00:00:00Z","timestamp":1562544000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["31003A-173183"],"award-info":[{"award-number":["31003A-173183"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Kyphoscoliotic Ehlers\u2013Danlos Syndrome (kEDS) is a rare genetic heterogeneous disease clinically characterized by congenital muscle hypotonia, kyphoscoliosis, and joint hypermobility. kEDS is caused by biallelic pathogenic variants in either PLOD1 or FKBP14. PLOD1 encodes the lysyl hydroxylase 1 enzyme responsible for hydroxylating lysyl residues in the collagen helix, which undergo glycosylation and form crosslinks in the extracellular matrix thus contributing to collagen fibril strength. FKBP14 encodes a peptidyl-prolyl cis\u2013trans isomerase that catalyzes collagen folding and acts as a chaperone for types III, VI, and X collagen. Despite genetic heterogeneity, affected patients with mutations in either PLOD1 or FKBP14 are clinically indistinguishable. We aim to better understand the pathomechanism of kEDS to characterize distinguishing and overlapping molecular features underlying PLOD1-kEDS and FKBP14-kEDS, and to identify novel molecular targets that may expand treatment strategies. Transcriptome profiling by RNA sequencing of patient-derived skin fibroblasts revealed differential expression of genes encoding extracellular matrix components that are unique between PLOD1-kEDS and FKBP14-kEDS. Furthermore, we identified genes involved in inner ear development, vascular remodeling, endoplasmic reticulum (ER) stress, and protein trafficking that were differentially expressed in patient fibroblasts compared to controls. Overall, our study presents the first transcriptomics data in kEDS revealing distinct molecular features between PLOD1-kEDS and FKBP14-kEDS, and serves as a tool to better understand the disease.<\/jats:p>","DOI":"10.3390\/genes10070517","type":"journal-article","created":{"date-parts":[[2019,7,10]],"date-time":"2019-07-10T03:05:26Z","timestamp":1562727926000},"page":"517","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Transcriptome Profiling of Primary Skin Fibroblasts Reveal Distinct Molecular Features Between PLOD1- and FKBP14-Kyphoscoliotic Ehlers\u2013Danlos Syndrome"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4201-1210","authenticated-orcid":false,"given":"Pei Jin","family":"Lim","sequence":"first","affiliation":[{"name":"Connective Tissue Unit, Division of Metabolism and Children\u2019s Research Centre, University Children\u2019s Hospital, 8032 Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uschi","family":"Lindert","sequence":"additional","affiliation":[{"name":"Connective Tissue Unit, Division of Metabolism and Children\u2019s Research Centre, University Children\u2019s Hospital, 8032 Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lennart","family":"Opitz","sequence":"additional","affiliation":[{"name":"Functional Genomics Center Zurich, University of Zurich\/ETH Zurich, Winterthurerstrasse 190, 8057 Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1095-4962","authenticated-orcid":false,"given":"Ingrid","family":"Hausser","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Heidelberg University Hospital, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4013-6012","authenticated-orcid":false,"given":"Marianne","family":"Rohrbach","sequence":"additional","affiliation":[{"name":"Connective Tissue Unit, Division of Metabolism and Children\u2019s Research Centre, University Children\u2019s Hospital, 8032 Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9313-8257","authenticated-orcid":false,"given":"Cecilia","family":"Giunta","sequence":"additional","affiliation":[{"name":"Connective Tissue Unit, Division of Metabolism and Children\u2019s Research Centre, University Children\u2019s Hospital, 8032 Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,7,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1002\/ajmg.c.31552","article-title":"The 2017 international classification of the Ehlers-Danlos syndromes","volume":"175","author":"Malfait","year":"2017","journal-title":"Am. J. Med. Genet. Part C Semin. Med. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/0076-6879(82)82067-3","article-title":"Posttranslational Enzymes in the Biosynthesis of Collagen: Intracellular Enzymes","volume":"82","author":"Kivirikko","year":"1982","journal-title":"Methods Enzymol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1038\/gim.2017.70","article-title":"A cohort of 17 patients with kyphoscoliotic Ehlers-Danlos syndrome caused by biallelic mutations in FKBP14: Expansion of the clinical and mutational spectrum and description of the natural history","volume":"20","author":"Giunta","year":"2018","journal-title":"Genet. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.ajhg.2011.12.004","article-title":"Mutations in FKBP14 cause a variant of Ehlers-Danlos syndrome with progressive kyphoscoliosis, myopathy, and hearing loss","volume":"90","author":"Baumann","year":"2012","journal-title":"Am. J. Hum. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"18189","DOI":"10.1074\/jbc.M114.561944","article-title":"A substrate preference for the rough endoplasmic reticulum resident protein FKBP22 during collagen biosynthesis","volume":"289","author":"Ishikawa","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/nrneurol.2011.81","article-title":"The collagen VI-related myopathies: Muscle meets its matrix","volume":"7","year":"2011","journal-title":"Nat. Rev. Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1002\/ajmg.a.30443","article-title":"Ullrich congenital muscular dystrophy: Connective tissue abnormalities in the skin support overlap with Ehlers-Danlos syndromes","volume":"132","author":"Kirschner","year":"2005","journal-title":"Am. J. Med. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.nmd.2007.11.006","article-title":"Differential diagnosis of muscular hypotonia in infants: The kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VI)","volume":"18","author":"Dirik","year":"2008","journal-title":"Neuromuscul. Disord."},{"key":"ref_9","unstructured":"Adam, M., Ardinger, H., and Pagon, R. (2019). FKBP14-Kyphoscoliotic Ehlers-Danlos Syndrome, University of Washington. GeneReviews."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Butterfield, R.J., Dunn, D.M., Hu, Y., Johnson, K., B\u00f6nnemann, C.G., and Weiss, R.B. (2017). Transcriptome profiling identifies regulators of pathogenesis in collagen VI related muscular dystrophy. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0189664"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.ymgme.2005.04.014","article-title":"Mutation analysis of the PLOD1 gene: An efficient multistep approach to the molecular diagnosis of the kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VIA)","volume":"86","author":"Giunta","year":"2005","journal-title":"Mol. Genet. Metab."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/1750-1172-6-46","article-title":"Phenotypic variability of the kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VIA): Clinical, molecular and biochemical delineation","volume":"6","author":"Rohrbach","year":"2011","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"W130","DOI":"10.1093\/nar\/gkx356","article-title":"WebGestalt 2017: A more comprehensive, powerful, flexible and interactive gene set enrichment analysis toolkit","volume":"45","author":"Wang","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"W741","DOI":"10.1093\/nar\/gki475","article-title":"WebGestalt: An integrated system for exploring gene sets in various biological contexts","volume":"33","author":"Zhang","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.ebiom.2016.10.012","article-title":"Collagen Matrix Density Drives the Metabolic Shift in Breast Cancer Cells","volume":"13","author":"Morris","year":"2016","journal-title":"EBioMedicine"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1038\/s42255-018-0008-5","article-title":"Metabolic regulation of dermal fibroblasts contributes to skin extracellular matrix homeostasis and fibrosis","volume":"1","author":"Zhao","year":"2019","journal-title":"Nat. Metab."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"13294","DOI":"10.1074\/jbc.M109.088864","article-title":"Interaction between periostin and BMP-1 promotes proteolytic activation of lysyl oxidase","volume":"285","author":"Maruhashi","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2028","DOI":"10.1074\/jbc.M109.051961","article-title":"Incorporation of tenascin-C into the extracellular matrix by periostin underlies an extracellular meshwork architecture","volume":"285","author":"Kii","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Nishiyama, T., Kii, I., Kashima, T.G., Kikuchi, Y., Ohazama, A., Shimazaki, M., Fukayama, M., and Kudo, A. (2011). Delayed re-epithelialization in periostin-deficient mice during cutaneous wound healing. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0018410"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1242\/jcs.087841","article-title":"Periostin modulates myofibroblast differentiation during full-thickness cutaneous wound repair","volume":"125","author":"Elliott","year":"2012","journal-title":"J. Cell Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1111\/j.1600-0625.2012.01454.x","article-title":"Periostin, a matricellular protein, accelerates cutaneous wound repair by activating dermal fibroblasts","volume":"21","author":"Ontsuka","year":"2012","journal-title":"Exp. Dermatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/s12079-010-0090-2","article-title":"Spatiotemporal expression of periostin during skin development and incisional wound healing: Lessons for human fibrotic scar formation","volume":"4","author":"Zhou","year":"2010","journal-title":"J. Cell Commun. Signal."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Yang, L., Serada, S., Fujimoto, M., Terao, M., Kotobuki, Y., Kitaba, S., Matsui, S., Kudo, A., Naka, T., and Murota, H. (2012). Periostin facilitates skin sclerosis via PI3K\/Akt dependent mechanism in a mouse model of scleroderma. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0041994"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1111\/bjd.12117","article-title":"Serum periostin levels are correlated with progressive skin sclerosis in patients with systemic sclerosis","volume":"168","author":"Yamaguchi","year":"2013","journal-title":"Br. J. Dermatol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2404","DOI":"10.1101\/gad.1230704","article-title":"Wnt\/\u03b2-catenin signaling is sufficient and necessary for synovial joint formation","volume":"18","author":"Guo","year":"2004","journal-title":"Genes Dev."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Strochlic, L., Falk, J., Goillot, E., Sigoillot, S., Bourgeois, F., Delers, P., Rouvi\u00e8re, J., Swain, A., Castellani, V., and Schaeffer, L. (2012). Wnt4 participates in the formation of vertebrate neuromuscular junction. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0029976"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1111\/j.1067-1927.2005.00069.x","article-title":"Differential expression and localization of WNTs in an animal model of skin wound healing","volume":"13","author":"Okuse","year":"2005","journal-title":"Wound Repair Regen."},{"key":"ref_28","first-page":"1059","article-title":"Wnt4 coordinates directional cell migration and extension of the m\u00fcllerian duct essential for ontogenesis of the female reproductive tract","volume":"25","author":"Skovorodkin","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1165\/ajrcmb.26.2.4666","article-title":"Transforming growth factor-\u03b2 stabilizes elastin mRNA by a pathway requiring active smads, protein kinase c-\u03b4, and p38","volume":"26","author":"Kucich","year":"2002","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2297","DOI":"10.1097\/01.prs.0000218708.16909.31","article-title":"Wnt-4 expression is increased in fibroblasts after TGF-beta1 stimulation and during fetal and postnatal wound repair","volume":"117","author":"Colwell","year":"2006","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1158\/0008-5472.CAN-15-2556","article-title":"Transcriptional Induction of Periostin by a Sulfatase 2-TGFb1-SMAD Signaling Axis Mediates Tumor Angiogenesis in Hepatocellular Carcinoma","volume":"77","author":"Chen","year":"2017","journal-title":"Cancer Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S0945-053X(01)00187-1","article-title":"Developmentally regulated expression of type XV collagen correlates with abnormalities in Col15a1-\/-mice","volume":"21","author":"Muona","year":"2002","journal-title":"Matrix Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1073\/pnas.98.3.1194","article-title":"Lack of type XV collagen causes a skeletal myopathy and cardiovascular defects in mice","volume":"98","author":"Eklund","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3059","DOI":"10.1093\/hmg\/ddm264","article-title":"Lack of fibulin-3 causes early aging and herniation, but not macular degeneration in mice","volume":"16","author":"McLaughlin","year":"2007","journal-title":"Hum. Mol. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1016\/j.bbrc.2009.12.034","article-title":"Fibulin-3 negatively regulates chondrocyte differentiation","volume":"391","author":"Wakabayashi","year":"2010","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Yao, H., Hill, S.F., Skidmore, J.M., Sperry, E.D., Swiderski, D.L., Sanchez, G.J., Bartels, C.F., Raphael, Y., Scacheri, P.C., and Iwase, S. (2018). CHD7 represses the retinoic acid synthesis enzyme ALDH1A3 during inner ear development. JCI Insight, 3.","DOI":"10.1172\/jci.insight.97440"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.ejvs.2012.08.004","article-title":"Spontaneous brachial pseudo-aneurysm in a 12-year-old with kyphoscoliosis-type ehlers-danlos syndrome","volume":"44","author":"Gok","year":"2012","journal-title":"Eur. J. Vasc. Endovasc. Surg."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1750","DOI":"10.1002\/ajmg.a.36492","article-title":"FKBP14-related Ehlers-Danlos syndrome: Expansion of the phenotype to include vascular complications","volume":"164","author":"Murray","year":"2014","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.1002\/ajmg.a.37728","article-title":"Further delineation of FKBP14-related Ehlers-Danlos syndrome: A patient with early vascular complications and non-progressive kyphoscoliosis, and literature review","volume":"170","author":"Dordoni","year":"2016","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/s00401-003-0714-1","article-title":"Capillary changes in skeletal muscle of patients with Ullrich\u2019s disease with collagen VI deficiency","volume":"106","author":"Niiyama","year":"2003","journal-title":"Acta Neuropathol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1161\/ATVBAHA.116.308606","article-title":"Olfactomedin 2 Regulates Smooth Muscle Phenotypic Modulation and Vascular Remodeling Through Mediating Runt-Related Transcription Factor 2 Binding to Serum Response Factor","volume":"37","author":"Shi","year":"2017","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0191220","article-title":"Transcriptome analysis of skin fibroblasts with dominant negative COL3A1 mutations provides molecular insights into the etiopathology of vascular Ehlers-Danlos syndrome","volume":"13","author":"Chiarelli","year":"2018","journal-title":"PLoS ONE"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3272","DOI":"10.1158\/0008-5472.CAN-08-4886","article-title":"The l6 protein TM4SF1 is critical for endothelial cell function and tumor angiogenesis","volume":"69","author":"Shih","year":"2009","journal-title":"Cancer Res."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Lisse, T.S., Thiele, F., Fuchs, H., Hans, W., Przemeck, G.K.H., Abe, K., Rathkolb, B., Quintanilla-Martinez, L., Hoelzlwimmer, G., and Helfrich, M. (2008). ER stress-mediated apoptosis in a new mouse model of Osteogenesis imperfecta. PLoS Genet., 4.","DOI":"10.1371\/journal.pgen.0040007"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"18226","DOI":"10.1016\/S0021-9258(17)46834-7","article-title":"BiP binds type I procollagen pro?? chains with mutations in the carboxyl-terminal propeptide synthesized by cells from patients with osteogenesis imperfecta","volume":"268","author":"Chessler","year":"1993","journal-title":"J. Biol. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"15544","DOI":"10.1074\/jbc.M410758200","article-title":"Misfolding of collagen X chains harboring schmid metaphyseal chondrodysplasia mutations results in aberrant disulfide bond formation, intracellular retention, and activation of the unfolded protein response","volume":"280","author":"Wilsoni","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"11318","DOI":"10.1074\/jbc.M807620200","article-title":"SCAMP5 links endoplasmic reticulum stress to the accumulation of expanded polyglutamine protein aggregates via endocytosis inhibition","volume":"284","author":"Noh","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Yang, Y., Qin, M., Bao, P., Xu, W., and Xu, J. (2017). Secretory carrier membrane protein 5 is an autophagy inhibitor that promotes the secretion of \u03b1-synuclein via exosome. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0180892"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1007\/s00223-016-0228-1","article-title":"Hypoxia-Induced Fibroblast Growth Factor 11 Stimulates Osteoclast-Mediated Resorption of Bone","volume":"100","author":"Knowles","year":"2017","journal-title":"Calcif. Tissue Int."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s13064-017-0083-4","article-title":"Semaphorin-Plexin signaling influences early ventral telencephalic development and thalamocortical axon guidance","volume":"12","author":"Mitsogiannis","year":"2017","journal-title":"Neural Dev."},{"key":"ref_51","first-page":"358","article-title":"Ehlers-Danlos Syndrome Type VI in a 17-Year-Old Iranian Boy with Severe Muscular Weakness\u2014A Diagnostic Challenge?","volume":"20","author":"Kariminejad","year":"2010","journal-title":"Iran. J. Pediatr."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"5479","DOI":"10.1128\/MCB.22.15.5479-5491.2002","article-title":"TAPP1 and TAPP2 are targets of phosphatidylinositol 3-kinase signaling in B-cells: Sustained plasma membrane recruitment triggered by the B-cell antigen receptor","volume":"22","author":"Marshall","year":"2002","journal-title":"Mol. Cell. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1042\/bj3610525","article-title":"Evidence that the tandem-pleckstrin-homology-domain-containing protein TAPP1 interacts with Ptd(3,4)P2 and the multi-PDZ-domain-containing protein MUPP1 in vivo","volume":"361","author":"Kimber","year":"2002","journal-title":"Biochem. J."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1002\/eji.201646596","article-title":"B-cell-intrinsic function of TAPP adaptors in controlling germinal center responses and autoantibody production in mice","volume":"47","author":"Jayachandran","year":"2017","journal-title":"Eur. J. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1556","DOI":"10.1016\/j.prp.2017.09.010","article-title":"The down-regulation of TAPP2 inhibits the migration of esophageal squamous cell carcinoma and predicts favorable outcome","volume":"213","author":"Liu","year":"2017","journal-title":"Pathol. Res. Pract."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Li, H., Hou, S., Wu, X., Nandagopal, S., Lin, F., Kung, S., and Marshall, A.J. (2013). The Tandem PH Domain-Containing Protein 2 (TAPP2) Regulates Chemokine-Induced Cytoskeletal Reorganization and Malignant B Cell Migration. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0057809"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/10\/7\/517\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:03:41Z","timestamp":1760187821000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/10\/7\/517"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,8]]},"references-count":56,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2019,7]]}},"alternative-id":["genes10070517"],"URL":"https:\/\/doi.org\/10.3390\/genes10070517","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,8]]}}}