Beta-Arrestin1 Promotes Colorectal Cancer Metastasis Through Gsk-3 Beta/Beta-Catenin Signaling-Mediated Epithelial-To-Mesenchymal Transition

Recurrence and metastasis seriously affects the prognosis of patients with tumors, and the epithelial-to-mesenchymal transition (EMT) plays a key role in promoting tumor invasion and metastasis. Previous studies have showed that beta-arrestin1 acted as a tumor-promoting factor in multiple types of tumor. However, the exact role and mechanism of beta-arrestin1 in colorectal cancer (CRC) progression remains to be elucidated. Our research aimed to explore the potential mechanism underlying the role of beta-arrestin1 in CRC metastasis. The expression of beta-arrestin1 was investigated in both primary and metastatic CRC tissues using the GSE41258 database, and it was revealed that CRC patients with liver/lung metastasis had a higher expression level of beta-arrestin1, and the expression level of beta-arrestin1 was inversely correlated with the prognosis of CRC patients. Further in vitro mechanism studies indicated that beta-arrestin1 had the ability to promote the migration of CRC cells through regulating the EMT process by activating Wingless/integration-1 (Wnt)/beta-catenin signaling pathways. Blocking Wnt/beta-catenin signaling with inhibitor ICG001 decreased the promoting effect of beta-arrestin1 on EMT in CRC. In vivo imaging experiments further demonstrated the promoting effect of beta-arrestin1 on the lung metastasis of CRC cells by tail vein injection in mice. The results of this paper suggest that beta-arrestin1 promotes EMT via Wnt/beta-catenin signaling pathway in CRC metastasis, and provides a novel therapeutic target for CRC metastasis.