Epithelial-to-mesenchymal transition（ EMT） is closely related to the development of malignancy in human oral squamous cell carcinoma（ hOSCC） cells. “Cadherin switch” refers to expression changes from E-cadherin to N-cadherin that occur during the malignant transformation of a cancer cell accompanying the EMT. The molecular mechanisms underlying the cadherin switch in hOSCC have not yet been fully elucidated. The Hippo pathway is known to transmit extracellular mechanical cues induced by changes in cell density, which in turn affect gene expression. Here, we found that the cadherin switch is induced at a low but not high cell density in the hOSCC cell line HSC-4. We also found that knockdown of YAP/TAZ, which is part of the Hippo pathway, increased E-cadherin expression but decreased N-cadherin expression in HSC-4 cells. The nuclear translocation of EMT-related transcription factor Slug was observed in HSC-4 cells at low cell density. In addition, low cell density-induced Slug nuclear translocation was inhibited by knockdown of YAP. Moreover, disruption of cell-to-cell adhesion with anti E-cadherin antibody promoted nuclear translocation of YAP, resulting in the cadherin switch in HSC-4 cells. These results suggested that YAP/TAZ mediates the low cell density-induced cadherin switch through nuclear translocation of Slug and that intercellular contact mediated by E-cadherin inhibits the cadherin switch through negative modulation of the Hippo pathway. Thus, disruption of E-cadherin mediated cell-to-cell contact-induced YAP/TAZ activation promotes cadherin switch through promotion of EMT-related transcription factor Slug nuclear translocation in hOSCC HSC-4 cells.
