IADR Abstract Archives
Desmoglein-3 Induces Phospho-YAP Expression and Controls Oral Cancer Cell Migration
Objectives: Alterations of the Hippo-YAP pathway are potential targets for oral squamous cell carcinoma (OSCC) therapy but heterogeneity in this pathway could be responsible for therapeutic resistance. The downstream effectors of this pathway, YAP/TAZ, are overexpressed in various cancers, including OSCC. However, the upstream regulators and their role in cancer progression remain not fully understood. Recent studies have revealed that Desmoglein-3 (DSG3) can regulate YAP, but on the other hand, YAP is also found to be able to influence DSG3 expression. Nevertheless, little is known about the role of this pathway in cell motility. This study aimed to investigate the molecular signatures of the Hippo-YAP pathway in a cohort of authenticated oral cell lines of normal, dysplasia and carcinoma, and the role of YAP in the metastatic potential of OSCC cells.
Methods: The expression of a panel of the genes and proteins in the Hippo-YAP pathway was evaluated in ten authenticated oral keratinocyte lines derived from the buccal and floor of mouth, by qPCR, Western blotting, and immunofluorescence. Cell migration was monitored by Oris migration/scratch wounding assays in cells with transient YAP knockdown or stable transduction of DSG3 (hDsg3.myc), with/without mitomycin C treatment.
Results: Heterogeneity of the Hippo-YAP pathway was detected in OSCC lines, including overexpression of YAP/TAZ and the major Hippo signalling components as well as the overall loss of intercellular junctional components. YAP depletion significantly suppressed cell migration ability with concomitantly enhanced DSG3 expression. Concordantly, DSG3 overexpression inactivated YAP via induction of phospho-YAP leading to repression of collective cell migration. Thus, this study identified mutually exclusive regulation between YAP and DSG3 in OSCC cells.
Conclusions: Our findings suggest that YAP is required for efficient OSCC cell migration via suppressing DSG3, a novel key component in the Hippo pathway that controls the contact inhibition of locomotion in OSCC cells.
Methods: The expression of a panel of the genes and proteins in the Hippo-YAP pathway was evaluated in ten authenticated oral keratinocyte lines derived from the buccal and floor of mouth, by qPCR, Western blotting, and immunofluorescence. Cell migration was monitored by Oris migration/scratch wounding assays in cells with transient YAP knockdown or stable transduction of DSG3 (hDsg3.myc), with/without mitomycin C treatment.
Results: Heterogeneity of the Hippo-YAP pathway was detected in OSCC lines, including overexpression of YAP/TAZ and the major Hippo signalling components as well as the overall loss of intercellular junctional components. YAP depletion significantly suppressed cell migration ability with concomitantly enhanced DSG3 expression. Concordantly, DSG3 overexpression inactivated YAP via induction of phospho-YAP leading to repression of collective cell migration. Thus, this study identified mutually exclusive regulation between YAP and DSG3 in OSCC cells.
Conclusions: Our findings suggest that YAP is required for efficient OSCC cell migration via suppressing DSG3, a novel key component in the Hippo pathway that controls the contact inhibition of locomotion in OSCC cells.