Tumor-associated macrophages (TAMs) depend on ZEB1 for their cancer-promoting roles.

ABSTRACT: Accumulation of tumor-associated macrophages (TAMs) associates with malignant progression in cancer. However, the mechanisms that drive the pro-tumor functions of TAMs are not fully understood. ZEB1 is best known for driving an epithelial-to-mesenchymal transition (EMT) in cancer cells to promote tumor progression. However, a role for ZEB1 in macrophages and TAMs has not been studied. Here we describe that TAMs require ZEB1 for their tumor-promoting and chemotherapy resistance functions in a mouse model of ovarian cancer. Only TAMs that expressed full levels of Zeb1 accelerated tumor growth. Mechanistically, ZEB1 expression in TAMs induced their polarization toward an F4/80^low pro-tumor phenotype, including direct activation of Ccr2 In turn, expression of ZEB1 by T

SUBMITTER: Cortes M 

PROVIDER: S-EPMC5686549 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature