Review Article

Epithelial-Mesenchymal Transition in Oral Squamous Cell Carcinoma

Figure 1

The pivotal role of E-cadherin, β-catenin, and transforming growth factor β (TGFβ) and Wnt signaling pathways in an epithelial-mesenchymal transition (EMT) program. Upon loss of E-cadherin expression, β-catenin, which colocalizes with E-cadherin at the cytoplasmic membrane, is released and accumulated in the cytoplasm. Under normal circumstances, liberated β-catenin is rapidly degraded by proteasomes in the adenomatous polyposis coli (APC)/axin/glycogen-synthase kinase 3β (GSK3β) complex. However, as in several cases of cancers, APC is not functional or the activity of GSK3β is diminished by the activation of Wnt signaling pathway, β-catenin can migrate to the nucleus, where it functions as a cofactor for the transcription factor T-cell factor (TCF) and potentiates its transcriptional activity in concert with the phosphorylated SMAD 2 and 3, triggered by TGFβ signaling, leading to tumor proliferation, EMT, migration, and invasion. Similar to β-catenin, p120-catenin can translocate into the nucleus, where it binds to the transcriptional repressor Kaiso to deactivate this protein, causing the unknown genes to become activated by derepression. GFs: growth factors; RTK: receptor tyrosine kinase; TGFβR: TGFβ receptor.
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