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Here, Laminin subunit gamma\u20102 (\n                    <jats:italic>LAMC2<\/jats:italic>\n                    ) with important oncogenic roles in iCCA is discovered. In a total of 231 cholangiocarcinoma patients (82% of iCCA patients) across four independent cohorts,\n                    <jats:italic>LAMC2<\/jats:italic>\n                    is significantly more abundant in iCCA tumor tissue compared to normal bile duct and non\u2010tumor liver. Among 26.3% of iCCA patients,\n                    <jats:italic>LAMC2<\/jats:italic>\n                    gene is amplified, contributing to its over\u2010expression. Functionally, silencing\n                    <jats:italic>LAMC2<\/jats:italic>\n                    significantly blocks tumor formation in orthotopic iCCA mouse models. Mechanistically, it promotes EGFR protein translation via interacting with nascent unglycosylated EGFR in the endoplasmic reticulum (ER), resulting in activated EGFR signaling.\n                    <jats:italic>LAMC2<\/jats:italic>\n                    \u2010mediated EGFR translation also depends on its interaction with the ER chaperone BiP via their C\u2010terminus. Together\n                    <jats:italic>LAMC2<\/jats:italic>\n                    and BiP generate a binding \u201cpocket\u201d of nascent EGFR and facilitate EGFR translation. Consistently,\n                    <jats:italic>LAMC2<\/jats:italic>\n                    \u2010high iCCA patients have poor prognosis in two iCCA cohorts.\n                    <jats:italic>LAMC2<\/jats:italic>\n                    \u2010high iCCA cells are highly sensitive to EGFR tyrosine kinase inhibitors (TKIs) treatment both in vitro and in vivo. Together, these data demonstrate\n                    <jats:italic>LAMC2<\/jats:italic>\n                    as an oncogenic player in iCCA by promoting EGFR translation and an indicator to identify iCCA patients who may benefit from available EGFR\u2010targeted TKIs therapies.\n                  <\/jats:p>","DOI":"10.1002\/advs.202309010","type":"journal-article","created":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T09:25:03Z","timestamp":1711358703000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Oncogenic Roles of Laminin Subunit Gamma\u20102 in Intrahepatic Cholangiocarcinoma via Promoting EGFR Translation"],"prefix":"10.1002","volume":"11","author":[{"given":"Jianjuan","family":"Zhang","sequence":"first","affiliation":[{"name":"The MOE Key Laboratory of Biosystems Homeostasis &amp; Protection Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology Life Sciences Institute Zhejiang University  Hangzhou Zhejiang 310058 China"},{"name":"Center for Life Sciences Shaoxing Institute Zhejiang University  Shaoxing Zhejiang 321000 China"},{"name":"Cancer Center Zhejiang University  Hangzhou Zhejiang 310058 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fubo","family":"Ji","sequence":"additional","affiliation":[{"name":"The MOE Key Laboratory of Biosystems Homeostasis &amp; 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