Translational study reveals that Mena downregulation suppresses metastasis in HPV16-positive oral cancer, indicating a mechanistic basis for differing clinical outcomes between HPV subtypes.
BACKGROUND: The objective of this study was to investigate the effect of mammalian-enabled protein (Mena) on invasion and metastasis of HPV16-related oral squamous cell carcinoma (OSCC) and the underlying mechanism. MATERIALS AND METHODS: The Mena gene expression profile of HPV-related OSCC was analyzed from the TCGA, GEO and TIMER databases. Immunohistochemistry was performed to study Mena, and the expression of invasion and metastasis-related markers and their clinicopathological characteristics. The role of Mena in the biological behavior of OSCC cell lines was assessed through both non-transfected and stably transfected models, analyzing EMT-related markers in vitro. The effect of Mena on HPV16-related OSCC metastasis through immunodeficient mouse model in vivo. RESULTS: Mena expression was significantly decreased in HPV16-positive OSCC, and Mena expression in HPV16-negative OSCC was related with lymphatic metastasis and TNM stages, and E-cadherin, vimentin and MMP-2, but it was not statistically significant in HPV16-positive OSCC. Increased Mena expression was significantly correlated with a poor overall survival and disease-free survival in an HPV16-negative OSCC patient. Mena plays a vital role in promoting OSCC cell migration, invasion and metastasis. CONCLUSIONS: Mena promotes OSCC invasion and metastasis in HPV-negative OSCC by activating the EMT process. However, Mena expression in OSCC infected with HPV16 is inhibited, thus suppressing its invasion and metastasis ability.
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