The Hippo signaling pathway comprises mammalian sterile 20-like kinase 1/2, large tumor suppressor 1/2, and Yes-associated protein 1 (YAP1). This study investigated phosphorylated YAP (pYAP, Ser 127) protein expression in oral squamous cell carcinoma (OSCC).

Tissues from patients with oral epithelial dysplasia (OED, n=7), carcinoma in situ (CIS, n=14), and OSCC (n=109) were analyzed.

Cytoplasmic expression of pYAP was low in OED, CIS, and OSCC tissues. The expression of pYAP was correlated with differentiation, and the expression of low levels of YAP was significantly more common in well-differentiated to moderately differentiated OSCC than in poorly differentiated OSCC. High pYAP expression correlates with characteristics of epithelial-to-mesenchymal transition (EMT), e.g., loss of E-cadherin and increased expression of vimentin and laminin 5 (p<0.0001). Additionally, the protein arginine methyltransferase 1, a positive modulatory factor of YAP activity, was found to be correlated with elevated levels of pYAP expression (p<0.0007).

The presence of elevated pYAP expression may serve as a prognostic indicator of an aggressive OSCC with EMT during the invasive stage.