Wnt/ß-catenin signalling, epithelial-mesenchymal transition and crosslink signalling in colorectal cancer cells.

ABSTRACT

Colorectal cancer (CRC), with its significant incidence and metastatic rates, profoundly affects human health. A common oncogenic event in CRC is the aberrant activation of the Wnt/ß-catenin signalling pathway, which drives both the initiation and progression of the disease. Persistent Wnt/ß-catenin signalling facilitates the epithelial-mesenchymal transition (EMT), which accelerates CRC invasion and metastasis. This review provides a summary of recent molecular studies on the role of the Wnt/ß-catenin signalling axis in regulating EMT in CRC cells, which triggers metastatic pathogenesis. We present a comprehensive examination of the EMT process and its transcriptional controllers, with an emphasis on the crucial functions of ß-catenin, EMT transcription factors (EMT-TFs). We also review recent evidences showing that hyperactive Wnt/ß-catenin signalling triggers EMT and metastatic phenotypes in CRC via "Destruction complex" of ß-catenin mechanisms. Potential therapeutic and challenges approache to suppress EMT and prevent CRC cells metastasis by targeting Wnt/ß-catenin signalling are also discussed. These include direct ß-catenin inhibitors and novel targets of the Wnt pathway, and finally highlight novel potential combinational treatment options based on the inhibition of the Wnt pathway.