Novel impacts of Fam3C in cancer-associated-adipocyte (CAA) within the tumor microenvironment (TME) of breast cancer

Abstract

Adipocyte is major constituents of tumor microenvironments (TME) in breast cancer. Nevertheless, the roles of cancer-associated-adipocytes (CAA) remain elusive. We found that the expression of Fam3C in CAA is upregulated by TGF-β signaling pathways. To determine the roles of Fam3C in CAA, Fam3C was overexpressed into 3T3-L1 adipocytes using adenoviral system. Fam3C overexpressing adipocytes increased cell survival when co-cultured with breast cancer cells. Furthermore, we established the Fam3C knock-out (Fam3C KO) 3T3-L1 pre-adipocytes by using the CRISPR-Cas9 system. When Fam3C Ko adipocytes co-cultured with breast cancer cells, they showed increase of cell death and promoted differentiation into fibroblast. These changes in adipocyte showed an inhibitory effect on breast cancer cells. The same effect was validated in the in vivo. Collectively, our findings demonstrated that a crosstalk between breast cancer cells and adipocytes through a TGF-β -Fam3C axis contributes to cell survival of both CAA and cancer cells