Role of Mesenchymal Markers in Colorectal Cancer Metastasis

Colorectal cancer (CRC) is the second most common cancer type that results in significant mortality, the primary cause of which is associated with metastasis. Epithelial-mesenchymal transition (EMT) is a biological process that converts polarized epithelial cells into migratory mesenchymal states, which is positively correlated with the dissemination of the tumor cells from the primary tumor site and is thus linked to metastasis. Mesenchymal markers are the proteins that are up-regulated upon initiation of EMT. This review aims to provide a comprehensive overview of the role of mesenchymal markers in CRC metastasis. Upon thorough data mining, fibronectin, vimentin, N-cadherin, and β-catenin were defined as the distinguished mesenchymal markers that are well-studied in the context of CRC metastasis. Expression of these markers was positively correlated with aggressive CRC stages. However, the underlying molecular mechanisms through which they facilitate CRC progression are partly explored. Fibronectin was reported to affect cell migration and invasion via NF-kB/p53 and ITGA5/FAK-P/RhoGTPase axis, while its Extra Domain A (EDA) regulates the lymphangiogenesis via VEGF-C/PI3K/AKT axis. For vimentin and N-cadherin, few upstream regulators have been reported; however, the downstream pathways via which they affect migration and invasion remain to be explored. β-catenin, a well explored molecule for CRC onset, has limited reports in relation to metastatic progression. Wnt/β-catenin signalling has been reported to promote migration and invasion in primary CRC, while it impedes the same in advanced CRC background. There are future scopes for mechanistic research on the underexplored mesenchymal markers, whereas the mechanistically explored molecules need to be tested clinically.