Adipocytes promote breast tumorigenesis through TAZ-dependent secretion of Resistin

Adipocytes have been implicated in breast tumor growth and stemness maintenance through secreted factors. However, the mechanisms by which these cytokines are regulated during dietinduced obesity and contribute to breast tumorigenesis remain largely unknown. Here we show that transcription cofactor...

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Veröffentlicht in:Proceedings of the National Academy of Sciences - PNAS 2020-12, Vol.117 (52), p.33295-33304
Hauptverfasser: Gao, Yuhao, Chen, Xiaosong, He, Qing, Gimple, Ryan C., Liao, Yajin, Wang, Liang, Wu, Rong, Xie, Qi, Rich, Jeremy N., Shen, Kunwei, Yuan, Zengqiang
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Sprache:eng
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Zusammenfassung:Adipocytes have been implicated in breast tumor growth and stemness maintenance through secreted factors. However, the mechanisms by which these cytokines are regulated during dietinduced 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/PPARγ 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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.2005950117