Adipocytes promote breast tumorigenesis through TAZ-dependent secretion of Resistin

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.