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Cell Dev. Biol."],"abstract":"<jats:p>Ectodermal neural cortex 1 (ENC1) is an actin-binding protein and has been known to be upregulated in several cancers, but the molecular mechanisms through which it contributes to the pathology of CRC have largely been elusive. We utilized data mining and validated the aberrant expression of ENC1, following which phenotypic traits of malignancy were assessed <jats:italic>in vitro<\/jats:italic>. Ruxolitinib was used as a surrogate to compare the effects of ENC1 expression and silencing on the JAK-STAT-AKT pathway. <jats:italic>In vivo<\/jats:italic> models were employed to confirm the <jats:italic>in vitro<\/jats:italic> observations. Computation analysis, strengthened by <jats:italic>in situ<\/jats:italic> and <jats:italic>in vitro<\/jats:italic> data, confirmed the overexpression of ENC1 in CRC and predicted a poor prognosis, while enhanced cell proliferation, invasion, migration, EMT, and stemness were associated with ENC1 overexpression. Silencing of ENC1 downregulated the phenotypes. Additionally, silencing of ENC1 significantly reduced the activation of JAK2 and consequent activation of STAT5 and AKT comparable to ruxolitinib inhibition of JAK2. Silencing of ENC1 resulted in lesser tumor volumes and fewer numbers of tumors, <jats:italic>in vivo<\/jats:italic>. These data suggest that ENC1 induces CRC through the JAK2-STAT5-AKT axis. ENC1 is a suitable diagnostic marker for CRC detection, and ENC1 targeting therapies may suppress CRC progression.<\/jats:p>","DOI":"10.3389\/fcell.2021.616887","type":"journal-article","created":{"date-parts":[[2021,3,16]],"date-time":"2021-03-16T05:26:24Z","timestamp":1615872384000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":22,"title":["ENC1 Facilitates Colorectal Carcinoma Tumorigenesis and Metastasis via JAK2\/STAT5\/AKT Axis-Mediated Epithelial Mesenchymal Transition and Stemness"],"prefix":"10.3389","volume":"9","author":[{"given":"Ying","family":"Cui","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiani","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yibing","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"QingWei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanfei","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingchun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqiao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,3,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2019.01284","article-title":"Biomarkers in colorectal cancer: the role of translational proteomics research","volume":"9","author":"Alves Martins","year":"2019","journal-title":"Front. 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