安普克
克拉斯
癌症研究
肺癌
生物
转录因子
背景(考古学)
蛋白激酶A
癌症
激酶
医学
细胞生物学
基因
病理
遗传学
结直肠癌
古生物学
作者
Lillian J. Eichner,Sonja N. Brun,Sébastien Herzig,Nathan P. Young,Stephanie D. Curtis,David B. Shackelford,Maxim N. Shokhirev,Mathias Leblanc,Liliana I. Vera,Amanda Hutchins,Debbie S. Ross,Reuben J. Shaw,Robert Svensson
出处
期刊:Cell Metabolism
[Elsevier]
日期:2019-02-01
卷期号:29 (2): 285-302.e7
被引量:148
标识
DOI:10.1016/j.cmet.2018.10.005
摘要
AMPK, a conserved sensor of low cellular energy, can either repress or promote tumor growth depending on the context. However, no studies have examined AMPK function in autochthonous genetic mouse models of epithelial cancer. Here, we examine the role of AMPK in murine KrasG12D-mediated non-small-cell lung cancer (NSCLC), a cancer type in humans that harbors frequent inactivating mutations in the LKB1 tumor suppressor-the predominant upstream activating kinase of AMPK and 12 related kinases. Unlike LKB1 deletion, AMPK deletion in KrasG12D lung tumors did not accelerate lung tumor growth. Moreover, deletion of AMPK in KrasG12D p53f/f tumors reduced lung tumor burden. We identified a critical role for AMPK in regulating lysosomal gene expression through the Tfe3 transcription factor, which was required to support NSCLC growth. Thus, AMPK supports the growth of KrasG12D-dependent lung cancer through the induction of lysosomes, highlighting an unrecognized liability of NSCLC.
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