TMEM16A enhances the activity of the Cdc42-NWASP signaling pathway to promote invasion and metastasis in oral squamous cell carcinoma

Abstract

ObjectiveTo explore the relationship between TMEM16A and metastasis and development in oral squamous cell carcinoma (OSCC). Study DesignDatabases GEPIA and UALCAN were employed to analyze the relationship between the expression of TMEM16A and the survival of oral cancer patients. TMEM16A was knocked down and overexpressed in CAL27 and SCC-4 cells, respectively, and the malignant behavior, and the expression of key proteins were detected. The Cdc42-NWASP pathway was inhibited, and the effects of TMEM16A and Cdc42-NWASP pathway on promoting the malignant behavior of cancer cells were verified. The xenograft tumor model was constructed, and tumor growth, cell proliferation index, apoptosis and Cdc42-NWASP signal pathway activity were detected. ResultsThe expression of TMEM16A in oral cancer tissues was significantly higher than that in adjacent tissues, and the patients with high expression of TMEM16A had shorter survival time. Overexpression of TMTM16A can significantly promote the occurrence of cancer and reduce the apoptosis of cancer cells, while the activity of Cdc42 pathway was higher. Knocking down TMEM16A or inhibiting Cdc42-NWASP pathway can reverse the above results. ConclusionThe activation of Cdc42-NWASP pathway by TMEM16A high expression is closely related to OSCC, which may become a new therapeutic target to prevent OSCC metastasis.