TRIM72 inhibits cell migration and epithelial-mesenchymal transition by attenuating FAK/Akt signalling in colorectal cancer

Abstract

Abstract TRIM72 (MG53) is a membrane repair protein with E3-ligase activity. In this study, we investigated its clinical significance and biological function in colorectal cancer (CRC). Reverse transcription-PCR was used to identify TRIM72 expression in primary CRC tumour tissue and the paired liver metastasis tumor samples. Results indicated that TRIM72 expression in paired liver metastases tissue was lower compared to the primary colon cancer tumour (p < 0.001). Aberrant expression of TRIM72 was significantly associated with the regional lymph node metastasis and clinical stage. Consistent with this, TRIM72 overexpression inhibited migration, intravasation and epithelial-mesenchymal transition of CRC cells in vitro and in vivo. In contrast, we found that TRIM72 knockdown significantly increased CRC cells' migration and invasion. Notably, we revealed that TRIM72 interacts with FAK and attenuate colon cancer metastasis by regulating FAK/Akt signalling pathway. Furthermore, patients with low expression of TRIM72 had poorer survival in two independent datasets. These findings indicate that TRIM72 plays a vital role in the metastasis of human colon cancer and possesses the potential to predict the survival of patients.