TIPE1 impairs stemness maintenance in colorectal cancer through directly targeting ß-catenin.

ABSTRACT

TIPE1 (tumor necrosis factor-α-induced protein 8-like 1) contributes to cell death in diverse cancers. However, the expression and biological functions of TIPE1 in colon cancer remain unclear. In the present study, we report that TIPE1 was downregulated in colon cancer tissues and positively correlates with prognosis of colon cancer patients. TIPE1 overexpression significantly inhibits colon cancer cell growth both in vitro and in vivo through impairing stemness, accompanied with downregulation of the stemness-related markers, ALDH, CD133, CD44 and SOX-9. Mechanically, TIPE1 directly targets ß-catenin and promotes ß-catenin degradation in a protease-dependent manner, and Wnt/ß-catenin signaling plays a crucial role during TIPE1-mediated stemness inhibition in colon cancer. These findings reveal that TIPE1 exerts anti-tumor effects in colon cancer and suggest that TIPE1 would be a therapeutic target for cancers.