Numb regulates cell proliferation and differentiation through endocytosis and ubiquitination of signaling molecules. Besides, Numb controls the migration of epithelial cells by regulating intercellular junctions. Studies have shown that Numb promotes or inhibits tumor progression in different tumors. However, its role and mechanism in colorectal cancer remain unclear. We found that the expression level of Numb in colon tumor tissues has a great variety in different patients. Numb expression was negatively correlated with TNM stage and lymph node metastasis but positively correlated with tumor size. Elevated expression of Numb was associated with a good prognosis. Inhibiting Numb expression promoted the migration and invasion of colon cancer cells induced by TGF-β, up-regulated the expression of EMT-related molecule Snail, and prevented the expression of E-cadherin. We also found that Numb promoted the proliferation and clones formation while inhibiting colon cancer cells' late apoptosis. In addition, Numb inhibited the RhoA activation and ROCK inhibitor Y-27632 or interfered with ROCK expression, partially inhibiting Numb-regulated cell proliferation and migration. In vivo tumorigenesis assay in nude mice also found that Numb promoted the proliferation of colon cancer cells, inhibited the expression of E-cadherin, and strengthened the expression of Snail. In conclusion, our study found that Numb plays multiple roles in the occurrence and progression of colon cancer by regulating the RhoA/ROCK signaling pathway, which provides a new theoretical molecular basis for the pathogenesis of colon cancer.
Keywords: Colon cancer; EMT; Numb; Rho-associated protein kinase; RhoA.
Copyright © 2021. Published by Elsevier Inc.