TG-interacting factor 1 mediates TNF-induced Ccl2 expression in adipocytes to promote prostate cancer progression.

Periprostatic adipose tissue secretes chemokines and lipid mediators that, particularly in the context of obesity, enhance prostate cancer cell (PCa) migration and invasion. Treating 3 T3-F442A pre-adipocytes with conditioned medium (CM) from M1-like RAW264.7 cells resulted in a significant upregulation of TG-interacting factor 1 (Tgif1) expression. Using a Tgif1 promoter reporter assay, we showed that the tumor necrosis factor (TNF) transcriptionally upregulates Tgif1 promoter activity, consistent with increased mRNA and protein expression. We also demonstrated that Tgif1 contributes to the modulation of TNF-driven Il-6 and Ccl2 cytokine mRNA expression in Tgif1-knockout and Tgif1-overexpressing 3 T3-F442A pre-adipocytes. CM from Tgif1-overexpressing cells showed a positive correlation between Tgif1 expression and PCa cell migration. We conclude that Tgif1 mediates TNF-induced Ccl2 expression in pre-adipocytes, thereby promoting PCa progression.