학술논문

Adipocytes promote breast tumorigenesis through TAZ-dependent secretion of Resistin
Document Type
Report
Source
Proceedings of the National Academy of Sciences of the United States. December 29, 2020, Vol. 117 Issue 52, p33295, 10 p.
Subject
United States
China
Language
English
ISSN
0027-8424
Abstract
Adipocytes have been implicated in breast tumor growth and stemness maintenance through secreted factors. However, the mechanisms by which these cytokines are regulated during diet-induced obesity and contribute to breast tumorigenesis remain largely unknown. Here we show that transcription cofactor TAZ in adipocytes is directly up-regulated by the free fatty acid/PPAR[gamma] axis upon dietary fat stimulation. TAZ knockdown alters the expression profile of a series of secreted proteins and attenuates the tumor-supporting function of adipocytes. Moreover, we identify Resistin, an adipose-derived hormone, as a functional downstream target of TAZ, which facilitates tumorigenesis, and its expression correlated with adipocyitc TAZ in triple-negative breast cancer samples. Further, Adiponectin-cre--mediated TAZ knockout in adipocytes mitigates breast tumor growth. Taken together, our findings highlight how diet-induced TAZ expression in adipocytes promotes tumorigenesis, suggesting promising cancer therapeutic targets. TAZ | Resistin | adipocyte | breast tumorigenesis