دورية أكاديمية
أعرض في EDS

YAP/TAZ and ATF4 drive resistance to Sorafenib in hepatocellular carcinoma by preventing ferroptosis.

التفاصيل البيبلوغرافية
العنوان: YAP/TAZ and ATF4 drive resistance to Sorafenib in hepatocellular carcinoma by preventing ferroptosis.
المؤلفون: Gao R; Department of Biomedicine, University of Basel, Basel, Switzerland., Kalathur RKR; Department of Biomedicine, University of Basel, Basel, Switzerland., Coto-Llerena M; Institute of Pathology, University Hospital Basel, Basel, Switzerland., Ercan C; Institute of Pathology, University Hospital Basel, Basel, Switzerland., Buechel D; Department of Biomedicine, University of Basel, Basel, Switzerland., Shuang S; Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland., Piscuoglio S; Institute of Pathology, University Hospital Basel, Basel, Switzerland., Dill MT; Stem Cell Program, Boston Children's Hospital, Boston, MA, USA.; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA., Camargo FD; Stem Cell Program, Boston Children's Hospital, Boston, MA, USA.; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA., Christofori G; Department of Biomedicine, University of Basel, Basel, Switzerland., Tang F; Department of Biomedicine, University of Basel, Basel, Switzerland.
المصدر: EMBO molecular medicine [EMBO Mol Med] 2021 Dec 07; Vol. 13 (12), pp. e14351. Date of Electronic Publication: 2021 Oct 19.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: EMBO Press Country of Publication: England NLM ID: 101487380 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1757-4684 (Electronic) Linking ISSN: 17574676 NLM ISO Abbreviation: EMBO Mol Med Subsets: MEDLINE
أسماء مطبوعة: Publication: 2024- : Heidelberg : EMBO Press
Original Publication: Chichester, West Sussex : Wiley-Blackwell
مواضيع طبية MeSH: Carcinoma, Hepatocellular*/pathology , Ferroptosis* , Liver Neoplasms*/pathology, Cell Cycle Proteins/*metabolism , Transcription Factors/*metabolism , Transcriptional Coactivator with PDZ-Binding Motif Proteins/*metabolism, Activating Transcription Factor 4/genetics ; Humans ; Sorafenib/pharmacology ; Transcription Factors/genetics
مستخلص: Understanding the mechanisms underlying evasive resistance in cancer is an unmet medical need to improve the efficacy of current therapies. In this study, a combination of shRNA-mediated synthetic lethality screening and transcriptomic analysis revealed the transcription factors YAP/TAZ as key drivers of Sorafenib resistance in hepatocellular carcinoma (HCC) by repressing Sorafenib-induced ferroptosis. Mechanistically, in a TEAD-dependent manner, YAP/TAZ induce the expression of SLC7A11, a key transporter maintaining intracellular glutathione homeostasis, thus enabling HCC cells to overcome Sorafenib-induced ferroptosis. At the same time, YAP/TAZ sustain the protein stability, nuclear localization, and transcriptional activity of ATF4 which in turn cooperates to induce SLC7A11 expression. Our study uncovers a critical role of YAP/TAZ in the repression of ferroptosis and thus in the establishment of Sorafenib resistance in HCC, highlighting YAP/TAZ-based rewiring strategies as potential approaches to overcome HCC therapy resistance.
(© 2021 The Authors. Published under the terms of the CC BY 4.0 license.)
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فهرسة مساهمة: Keywords: ATF4; Hippo signaling; YAP/TAZ; ferroptosis; liver cancer
المشرفين على المادة: 0 (ATF4 protein, human)
0 (Cell Cycle Proteins)
0 (Transcription Factors)
0 (Transcriptional Coactivator with PDZ-Binding Motif Proteins)
0 (YY1AP1 protein, human)
145891-90-3 (Activating Transcription Factor 4)
9ZOQ3TZI87 (Sorafenib)
تواريخ الأحداث: Date Created: 20211019 Date Completed: 20220311 Latest Revision: 20240404
رمز التحديث: 20240404
مُعرف محوري في PubMed: PMC8649869
DOI: 10.15252/emmm.202114351
PMID: 34664408
قاعدة البيانات: MEDLINE
الوصف
تدمد:1757-4684
DOI:10.15252/emmm.202114351