{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T12:15:59Z","timestamp":1786450559281,"version":"build-2736575974"},"reference-count":37,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,3,3]],"date-time":"2019-03-03T00:00:00Z","timestamp":1551571200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["16441906903"],"award-info":[{"award-number":["16441906903"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007219","name":"Natural Science Foundation of Shanghai","doi-asserted-by":"publisher","award":["16ZR1420400"],"award-info":[{"award-number":["16ZR1420400"]}],"id":[{"id":"10.13039\/100007219","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:sec><jats:label\/><jats:p>Epidermal growth factor\u2010like protein 6 (EGFL6) serves as an exocrine protein promoting proliferation and migration during carcinogenesis in ovarian cancer. However, its function and mechanisms in colorectal cancer (CRC) have not been completely explored. To investigate the role of EGFL6 in CRC cell growth, in vitro CCK8, colony formation assays, flow cytometric analysis of the cell cycle and apoptosis, and an in vivo tumor xenograft model were utilized. Additionally, Western blotting and luciferase reporter assays were used to investigate the underlying mechanisms of EGFL6 function on the WNT\/\u03b2\u2010catenin signaling pathway. Immunohistochemical staining showed that EGFL6 is overexpressed in CRCs and this overexpression was highly correlated with advanced T classification, N classification, distant metastasis, and poor survival. Knocking down EGFL6 in CRC cell lines induced the inhibition of cell growth, cell cycle arrest at the G0\/G1 phase, and apoptosis. Further, knockdown of EGFL6 blocked WNT\/\u03b2\u2010catenin signaling as measured by Western blotting and luciferase reporter assay. Results also showed that recombinant EGFL6 (rEGFL6) induced \u03b2\u2010catenin in a concentration\u2010 and time\u2010dependent manner. Further experiments showed that administration of rEGFL6 to cell cultures with EGFL6 knocked down or treated with the WNT\/\u03b2\u2010catenin inhibitor ICG\u2010001 increased \u03b2\u2010catenin and its downstream protein CyclinD1. The CCK8 assay showed that EGFL6 promoted CRC cell growth partly by the promotion of TCF7L2 expression. These findings suggest that EGFL6 plays a crucial role in the progression of CRC by regulation of the WNT\/\u03b2\u2010catenin signaling pathway.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mc.22985","type":"journal-article","created":{"date-parts":[[2019,1,29]],"date-time":"2019-01-29T18:29:17Z","timestamp":1548786557000},"page":"967-979","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["EGFL6 promotes cell proliferation in colorectal cancer via regulation of the WNT\/\u03b2\u2010catenin pathway"],"prefix":"10.1002","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6908-049X","authenticated-orcid":false,"given":"Qing\u2010Wei","family":"Zhang","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai Institute of Digestive Disease Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin\u2010Tian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai Institute of Digestive Disease Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao\u2010Tao","family":"Tang","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai Institute of Digestive Disease Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9994-1537","authenticated-orcid":false,"given":"Xiao\u2010Lu","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Digestive Endoscopy, Provincial Clinic Medical College, Fujian Medical University Fujian Provincial Hospital Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi\u2010Zheng","family":"Ge","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai Institute of Digestive Disease Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao\u2010Bo","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai Institute of Digestive Disease Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,3,3]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21387"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djh275"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.16829"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2013-306503"},{"key":"e_1_2_11_6_1","unstructured":"ForceUSPST Bibbins\u2010DomingoK GrossmanDC et al. 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