In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 117, No. 52 ( 2020-12-29), p. 33295-33304
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/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.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.2005950117
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2020
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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