Open AccessAdipocytes promote breast tumorigenesis through TAZ-dependent secretion of Resistin
Author(s) -
Yuhao Gao,
Xiaosong Chen,
Qing He,
Ryan C. Gimple,
Yuhe Liao,
Liang Wang,
Rong Wu,
Qi Xie,
Jeremy Rich,
Kunwei Shen,
Zengqiang Yuan
Publication year - 2020
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2005950117
Subject(s) - resistin , medicine , endocrinology , downregulation and upregulation , gene knockdown , carcinogenesis , cancer research , breast cancer , secretion , adipose tissue , adipocyte , immunostaining , biology , tumor microenvironment , cancer , leptin , adipokine , obesity , immunohistochemistry , cell culture , biochemistry , gene , genetics
Significance Adipocytes are the most abundant and perhaps most active components of the tumor microenvironment in obese individuals that potentiate breast tumorigenesis through secretory mechanisms. The modulation of adipocytes can be novel therapy targets for breast cancer. Here, we revealed a specific upregulation of adipocytic TAZ through the FFA/PPARγ axis in diet-induced adiposity. Adipocytic TAZ knockdown or deficiency in mice inhibits adipocyte-induced breast cancer proliferation and stemness through impaired expression and secretion of Resistin. Immunostaining in triple-negative breast cancer samples showed that higher adipocytic TAZ/Resistin expression associates with higher clinical stages and poorer survival, demonstrating promising therapeutic targets.