脂肪组织
脂肪细胞
骨桥蛋白
mTORC1型
生物
肿瘤微环境
癌变
串扰
癌症研究
癌症
体内
内分泌学
内科学
细胞生物学
信号转导
PI3K/AKT/mTOR通路
医学
肿瘤细胞
生物技术
物理
光学
遗传学
作者
Jianfeng Huang,Abraham Madroñal Durán,Miguel Reina-Campos,Tania Valencia,Elias A. Castilla,Timo Müller,Matthias H. Tschöp,Jorge Moscat,Marı́a T. Diaz-Meco
出处
期刊:Cancer Cell
[Elsevier]
日期:2018-04-01
卷期号:33 (4): 770-784.e6
被引量:80
标识
DOI:10.1016/j.ccell.2018.03.001
摘要
Obesity is a leading risk factor for cancer. However, understanding the crosstalk between adipocytes and tumor cells in vivo, independently of dietary contributions, is a major gap in the field. Here we used a prostate cancer (PCa) mouse model in which the signaling adaptor p62/Sqstm1 is selectively inactivated in adipocytes. p62 loss in adipocytes results in increased osteopontin secretion, which mediates tumor fatty acid oxidation and invasion, leading to aggressive metastatic PCa in vivo. Furthermore, p62 deficiency triggers in adipocytes a general shutdown of energy-utilizing pathways through mTORC1 inhibition, which supports nutrient availability for cancer cells. This reveals a central role of adipocyte's p62 in the symbiotic adipose tissue-tumor collaboration that enables cancer metabolic fitness.
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