Tripartite motif-containing protein 6 facilitates growth and migration of breast cancer through degradation of STUB1.

Abstract

Proteins in the tripartite motif-containing protein (TRIM) family participate in carcinogenesis. However, little attention was paid to the role of TRIM6 in development of breast cancer. Our results showed that the expression level of TRIM6 was found to be markedly enhanced in breast cancer cells and tissues. Functional assays demonstrated that overexpression of TRIM6 promoted breast cancer progression through increasing the expression of YAP1 (Yes-associated Protein 1), while knockdown of TRIM6 suppressed in vitro breast cancer progression and in vivo tumor growth through decreasing of YAP1. Co-Immunoprecipitation showed that TRIM6 interacted with STUB1 (stress induced phosphoprotein 1 homology and U-box containing protein 1). TRIM6 promoted ubiquitination-mediated degradation of STUB1 thereby promoting YAP1 signaling. Overexpression of STUB1 attenuated TRIM6-induced promotion of breast cancer growth. In conclusion, TRIM6 contributed to breast cancer progression through ubiquitination-dependent proteasomal degradation of STUB1 and provocation of YAP1 pathway, providing potential therapeutic target for breast cancer.