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β诱导的胰腺癌细胞转化

作者:葡京赌城真人发布时间:2020-09-26 18:58

本期文章:《癌细胞》:Online/在线发表

美国福克斯蔡斯癌症中心Igor Astsaturov组的最新研究表明,抑制胆固醇途径诱导的TGF-β信号促进胰腺癌细胞的基础分化。相关论文在线发表在2020年9月24日的《癌细胞》杂志上。

 

研究人员发现胆固醇代谢决定胰腺导管腺癌(PDAC)的发育和分化。在表达KrasG12D和纯合Trp53缺失的小鼠模型中,条件性灭活限速酶Nsdhl或利用降胆固醇他汀类药物破坏远端胆固醇的合成导致腺胰腺癌转化为基础(间质)表型。与此一致,接受他汀类药物治疗的患者中PDAC表现出间充质增强的表型。

 

从机制上讲,他汀类药物和NSDHL的丢失会诱导SREBP1的活化,从而促进Tgfb1的表达,从而实现上皮-间质转化。来自患者样本的证据表明,降胆固醇他汀类药物可激活转化生长因子β信号和上皮-间质转化,这可能促进PDAC基础型的出现,造成患者的不良预后。

 

附:英文原文

 

Title:Cholesterol Pathway Inhibition Induces TGF-β Signaling to Promote Basal Differentiation in Pancreatic Cancer

 

Author:Linara Gabitova-Cornell Aizhan Surumbayeva Suraj Peri Erica A. Golemis Edna Cukierman Igor Astsaturov

 

Issue&Volume:September 24, 2020

 

Abstract: Oncogenic transformation alters lipid metabolism to sustain tumor growth. We define a mechanism by which cholesterol metabolism controls the development and differentiation of pancreatic ductal adenocarcinoma (PDAC). Disruption of distal cholesterol biosynthesis by conditional inactivation of the rate-limiting enzyme Nsdhl or treatment with cholesterol-lowering statins switches glandular pancreatic carcinomas to a basal (mesenchymal) phenotype in mouse models driven by Kras G12D expression and homozygous Trp53 loss. Consistently, PDACs in patients receiving statins show enhanced mesenchymal features. Mechanistically, statins and NSDHL loss induce SREBP1 activation, which promotes the expression of Tgfb1, enabling epithelial-mesenchymal transition. Evidence from patient samples in this study suggests that activation of transforming growth factor β signaling and epithelial-mesenchymal transition by cholesterol-lowering statins may promote the basal type of PDAC, conferring poor outcomes in patients.

 

DOI:https://doi.org/10.1016/j.ccell.2020.08.015

 

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(20)30426-8

期刊信息

Cancer Cell:《癌细胞》,创刊于2002年。隶属于细胞出版社,最新IF:23.916
官方网址:https://www.cell.com/cancer-cell/home
投稿链接:https://www.editorialmanager.com/cancer-cell/default.aspx

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