| |  Online-Ressource |
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| Verfasst von: | Zhang, Jianjuan [VerfasserIn]  |
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| | Ji, Fubo [VerfasserIn] |
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| | Tan, Yaqi [VerfasserIn] |
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| | Zhao, Lei [VerfasserIn] |
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| | Zhao, Yongzhi [VerfasserIn] |
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| | Liu, Jiaxin [VerfasserIn] |
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| | Shao, Liyuan [VerfasserIn] |
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| | Shi, Jiong [VerfasserIn] |
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| | Ye, Meihua [VerfasserIn] |
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| | He, Xianglei [VerfasserIn] |
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| | Jin, Jianping [VerfasserIn] |
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| | Zhao, Bin [VerfasserIn] |
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| | Huang, Jun [VerfasserIn] |
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| | Rössler, Stephanie [VerfasserIn] |
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| | Zheng, Xin [VerfasserIn] |
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| | Ji, Junfang [VerfasserIn] |
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| Titel: | Oncogenic roles of laminin subunit gamma-2 in intrahepatic cholangiocarcinoma via promoting EGFR translation |
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| Verf.angabe: | Jianjuan Zhang, Fubo Ji, Yaqi Tan, Lei Zhao, Yongzhi Zhao, Jiaxin Liu, Liyuan Shao, Jiong Shi, Meihua Ye, Xianglei He, Jianping Jin, Bin Zhao, Jun Huang, Stephanie Roessler, Xin Zheng, and Junfang Ji |
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| E-Jahr: | 2024 |
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| Jahr: | June 5, 2024 |
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| Umfang: | 18 S. |
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| Illustrationen: | Illustrationen |
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| Fussnoten: | Zuerst veröffentlicht: 25. März 2024 ; Gesehen am 22.08.2024 |
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| Titel Quelle: | Enthalten in: Advanced science |
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| Ort Quelle: | Weinheim : Wiley-VCH, 2014 |
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| Jahr Quelle: | 2024 |
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| Band/Heft Quelle: | 11(2024), 21 vom: Juni, Artikel-ID 2309010, Seite 1-18 |
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| ISSN Quelle: | 2198-3844 |
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| Abstract: | Intrahepatic cholangiocarcinoma (iCCA) is a highly lethal biliary epithelial cancer in the liver. Here, Laminin subunit gamma-2 (LAMC2) with important oncogenic roles in iCCA is discovered. In a total of 231 cholangiocarcinoma patients (82% of iCCA patients) across four independent cohorts, LAMC2 is significantly more abundant in iCCA tumor tissue compared to normal bile duct and non-tumor liver. Among 26.3% of iCCA patients, LAMC2 gene is amplified, contributing to its over-expression. Functionally, silencing LAMC2 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. LAMC2-mediated EGFR translation also depends on its interaction with the ER chaperone BiP via their C-terminus. Together LAMC2 and BiP generate a binding “pocket” of nascent EGFR and facilitate EGFR translation. Consistently, LAMC2-high iCCA patients have poor prognosis in two iCCA cohorts. LAMC2-high iCCA cells are highly sensitive to EGFR tyrosine kinase inhibitors (TKIs) treatment both in vitro and in vivo. Together, these data demonstrate LAMC2 as an oncogenic player in iCCA by promoting EGFR translation and an indicator to identify iCCA patients who may benefit from available EGFR-targeted TKIs therapies. |
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| DOI: | doi:10.1002/advs.202309010 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
kostenfrei: Volltext: https://doi.org/10.1002/advs.202309010 |
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| | kostenfrei: Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/advs.202309010 |
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| | DOI: https://doi.org/10.1002/advs.202309010 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | EGFR |
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| | glycosylation |
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| | intrahepatic cholangiocarcinoma |
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| | LAMC2 |
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| | protein translation |
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| K10plus-PPN: | 1899361472 |
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| Verknüpfungen: | → Zeitschrift |
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Oncogenic roles of laminin subunit gamma-2 in intrahepatic cholangiocarcinoma via promoting EGFR translation / Zhang, Jianjuan [VerfasserIn]; June 5, 2024 (Online-Ressource)
