Wnt/β-catenin signaling and oral cancer metastasis

The Wnt/β-catenin signaling pathway participates in many physiologic events in embryogenesis and adult homeostasis, including cell fate specification, maintenance, and activation of stem cells. Dysregulation of Wnt/β-catenin signaling promotes uncontrolled cell growth, survival, and consequently results in epithelial-to-mesenchymal transition (EMT) and the development of familial and/or sporadic epithelial cancers in a range of tissues such as colon, skin, liver, and ovary cancers. In squamous cell carcinoma of the oral cavity, SCCOC, its roles, however, are largely undefined. Although it is evident that constitutive activation of the Wnt/β-catenin is frequently observed in oral cancer progression, only infrequent mutations have been found in genes encoding various components of this pathway that commonly mutated in other cancers. This suggests that Wnt/β-catenin signaling is probably activated by multiple mechanisms, including genetic and epigenetic alterations of the components in this signaling, and the alterations in other autocrine and/or paracrine factors that are involved in the regulation of this pathway. More importantly, the interaction between epithelial tumor cells and the different components of the surrounding microenvironment can locally affect the intracellular levels of Wnt/β-catenin signaling components and differentially trigger tumor cell stemness, cell proliferation, EMT, invasive behavior, and metastasis. The exact mechanisms by which this occurs still remain unclear. Therefore, further investigation is required for understanding the role of Wnt/β-catenin signaling in the tumorigenesis, tumor progression, and metastasis of SCCOC.