Adipocytes promote breast cancer tumorigenesis through TAZ-dependent paracrine secretion of Resistin. Mus musculus

Adipocytes have been implicated in breast tumor growth and stemness maintenence through secreted factors. However, the mechanisms by which these cytokines are regulated during obesity and contribute to breast cancer remains largely unknown. Here we show that transcription co-factor TAZ in adipocytes is directly upregulated by free fatty acid /PPARγ 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 acts to promote tumorigenesis, and is correlated with TAZ in samples from triple-negative breast cancer patients. Further, Adiponectin-cre mediated TAZ knockout or treatment with a Resistin blocking antibody mitigates tumor growth. Taken together, our findings highlight how diet-induced TAZ expression in adipocytes promotes tumorigenesis, suggesting promising cancer therapeutic targets.