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科学家揭示PKCλι缺失促进肝癌进展的机制
作者:小柯机器人 发布时间:2020/6/28 11:52:27

美国Sanford Burnham Prebys医学发现研究所Jorge Moscat及其研究团队发现,蛋白激酶C(PKC)λ/ι丢失诱导自噬、氧化磷酸化,NRF2促进肝癌(HCC)进展。这一研究成果在线发表在2020年6月25日的《癌细胞》上。

研究人员发现肝细胞中蛋白激酶C(PKC)λ/ι的丢失促进自噬和氧化磷酸化。这导致了活性氧(ROS)的产生,ROS通过NRF2以细胞自主和非自主机制诱发HCC。尽管在癌基因诱发癌症的模型中PKCλ/ a促进肿瘤发生,但是新证据表明它在更复杂的致癌过程中是肿瘤抑制因子。与此一致,PKCλ/ι水平与HCC组织学肿瘤分级呈负相关,从而认定该激酶在肝癌中为肿瘤抑制因子。

据悉,氧化应激在肝组织损伤和HCC的发生和发展中起着至关重要的作用。但是,仍然需要充分了解调控ROS生成过程中自噬和代谢重编程的机制以及ROS如何促进肿瘤发生。

附:英文原文

Title: PKCλ/ι Loss Induces Autophagy, Oxidative Phosphorylation, and NRF2 to Promote Liver Cancer Progression

Author: Yotaro Kudo, Masayuki Sugimoto, Esperanza Arias, Hiroaki Kasashima, Thekla Cordes, Juan F. Linares, Angeles Duran, Yuki Nakanishi, Naoko Nakanishi, Antoine LHermitte, Alex Campos, Nadia Senni, Tarmo Rooslid, Lewis R. Roberts, Ana Maria Cuervo, Christian M. Metallo, Michael Karin, Maria T. Diaz-Meco, Jorge Moscat

Issue&Volume: 2020-06-25

Abstract: Oxidative stress plays a critical role in liver tissue damage and in hepatocellularcarcinoma (HCC) initiation and progression. However, the mechanisms that regulateautophagy and metabolic reprogramming during reactive oxygen species (ROS) generation,and how ROS promote tumorigenesis, still need to be fully understood. We show thatprotein kinase C (PKC) λ/ι loss in hepatocytes promotes autophagy and oxidative phosphorylation.This results in ROS generation, which through NRF2 drives HCC through cell-autonomousand non-autonomous mechanisms. Although PKCλ/ι promotes tumorigenesis in oncogene-drivencancer models, emerging evidence demonstrate that it is a tumor suppressor in morecomplex carcinogenic processes. Consistently, PKCλ/ι levels negatively correlate withHCC histological tumor grade, establishing this kinase as a tumor suppressor in livercancer.

DOI: 10.1016/j.ccell.2020.05.018

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(20)30268-3

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