Wnt/-catenin-driven EMT regulation in human cancers

Metastasis accounts for 90% of cancer-related deaths among the patients. The transformation of epithelial cells into mesenchymal cells with molecular alterations can occur during epithelial-mesenchymal transition (EMT). The EMT mechanism accelerates the cancer metastasis and drug resistance ability in human cancers. Among the different regulators of EMT, Wnt/beta-catenin axis has been emerged as a versatile modulator. Wnt is in active form in physiological condition due to the function of GSK-3 beta that destructs beta-catenin, while ligand-receptor interaction impairs GSK-3 beta function to increase beta-catenin stability and promote its nuclear transfer. Regarding the oncogenic function of Wnt/beta-catenin, its upregulation occurs in human cancers and it can accelerate EMT-mediated metastasis and drug resistance. The stimulation of Wnt by binding Wnt ligands into Frizzled receptors can enhance beta-catenin accumulation in cytoplasm that stimulates EMT and related genes upon nuclear translocation. Wnt/beta-catenin/EMT axis has been implicated in augmenting metastasis of both solid and hematological tumors. The Wnt/EMT-mediated cancer metastasis promotes the malignant behavior of tumor cells, causing therapy resistance. The Wnt/beta-catenin/EMT axis can be modulated by upstream mediators in which non-coding RNAs are main regulators. Moreover, pharmacological intervention, mainly using phytochemicals, suppresses Wnt/EMT axis in metastasis suppression.