[Yes-associated protein (YAP) promotes invasion and migration of cutaneous squamous cell carcinoma cells by activating the PI3K/AKT pathway].

Objective To investigate the expression of Yes-associated protein (YAP) in cutaneous squamous cell carcinoma (cSCC) and its effects on invasion and migration. Methods Immunohistochemical staining was used to detect the expression of YAP in cSCC, Bowen disease (BD), and adjacent normal tissues, and analyzed the correlation between YAP expression and clinicopathological characteristics of cSCC. A stable cell line in A431 cells with YAP gene silencing was established through lentiviral infection. Tetramethylrhodamine isothiocyanate (TRITC)-phalloidin staining was performed to analyze the distribution and number of microfilaments in A431 cells. Transwell chamber assay was performed to detect the invasion ability of cells, and scratch healing assay was used to determine the migration ability. Immunofluorescence cytochemistry was used to detected the expression of EMT-related markers, including epithelial-cadherin (E-cadherin), zinc-finger transcription factors Snail in A431 cells with YAP silencing. Western blot analysis was employed to detect the expression of E-cadherin, snail, β-catenin, phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), phosphorylaedAKT (p-AKT), ribosomal proteinS6(S6), phosphorylatedS6 (p-S6), 4E-binding protein 1 (4EBP1), and phosphorylated 4EBP1 (p-4EBP1). ResultsThe expression of YAP was significantly higher in BD and cSCC tissues compared to adjacent tissues. The strong positive rate of YAP in cSCC tissues was associated with tumor size, differentiation and the level of invasion. However, there was no correlation between YAP expression and gender, age, tumor location, morphological type, or nerve and vascular invasion. After silencing the expression of YAP in A431 cells, the migration and invasion ability of tumor cells were significantly reduced, and cell microfilaments became thinner with reduced pseudopodia. The expression of E-cadherin was increased, while the expression of snail, β-catenin, p-AKT, p-S6 and p-4EBP1were decreased. Conclusion YAP is highly expressed in cSCC tissues, and promotes the cell migration and invasion of cSCC cells by activating the PI3K/AKT signaling pathway and EMT.