Knockdown of TRIM47 inhibits breast cancer tumorigenesis and progression through the inactivation of PI3K/Akt pathway

Abstract

Tripartite motif (TRIM) protein family is a group of proteins, which belongs to RING family of ubiquitin E3 ligases. TRIM proteins are involved in oncogenesis, while the roles in different cancers are controversial. However, the expression pattern and biological functions of TRIM47 in breast cancer remain unclear. In the present study, we aimed to investigate the function of TRIM47 in the progression and metastasis of breast cancer. TRIM47 was found to be significantly up-regulated in breast cancer tissues and cell lines. TRIM47 knockdown in breast cancer cell lines significantly inhibited cell proliferation, migration, and invasion. Besides, TRIM47 knockdown regulated the expressions of the epithelial-mesenchymal transition (EMT)-related markers including increase in E-cadherin, and decrease in N-cadherin, vimentin and Snail. Xenograft tumor assay proved that TRIM47 knockdown also suppressed tumor growth in vivo. Furthermore, TRIM47 knockdown markedly inhibited the activation of PI3K/Akt signaling pathway, while the effects of TRIM47 knockdown were reversed by the treatment of insulin-like growth factor-1 (IGF-1), which is an activator of PI3K/Akt. Taken together, the findings indicated that knockdown of TRIM47 suppressed tumorigenesis and progression of breast cancer through the inhibition of PI3K/Akt pathway, and suggested that TRIM47 might be a potential therapy target for breast cancer treatment.