WAVE3 Facilitates the Tumorigenesis and Metastasis of Tongue Squamous Cell Carcinoma via EMT.

Wiskott-Aldrich syndrome protein family verprolin-homologous domain-containing protein 3 (WAVE3) is reported as an oncogene regulating cell proliferation and motility in multiple malignancies, while its role in tongue squamous cell carcinoma (TSCC) remains unknown. This study aimed to explore the expression and mechanism of WAVE3 in TSCC. We enrolled 64 TSCC patients admitted between June 2013 and February 2014 and collected their cancerous and adjacent normal tissues to determine WAVE3 expression by immunohistochemistry. The correlation of WAVE3 expression with TSCC patients' pathological characteristics was analyzed. Then, a 7-year follow-up was conducted to observe the value of WAVE3 in evaluating patient outcomes. In addition, human TSCC SCC9, SCC25, and CAL27 cells were purchased and detected by Cell Counting Kit-8 (CCK-8), Transwell, and scratch-wound assays for their proliferation, invasion, and migration capacities, while real-time quantitative PCR (qRT-PCR) and Western blotting were utilized to quantify WAVE3 and epithelial-mesenchymal transition (EMT)-related protein expression, respectively. The most active cell lines were selected to be infected with lentiviral vectors that silenced WAVE3 (named WAVE3-sh group) and overexpressed WAVE3 cDNA (named WAVE3-OE group) to observe the impacts of interfering WAVE3 expression on TSCC cell biological behavior. The positive expression of WAVE3 in TSCC tissue was found to be obviously enhanced and predominantly located in the cytoplasm. In addition, close correlations were identified between WAVE3 and T staging, clinical staging, lymphatic metastasis, distant metastasis, and differentiation degree (P < 0.05). Increased WAVE3 expression predicted an elevated risk of death, as indicated by the follow-up analysis (P < 0.05). SCC9 was selected for subsequent experiments among various TSCC cell lines studied because it showed the most potent ability to proliferate, invade, and migrate (P < 0.05). Silencing WAVE3 expression in SCC9 cells decreased cell proliferation, invasion, migration, and EMT-related protein expression (P < 0.05), while increasing WAVE3 expression promoted SCC9 viability. WAVE3, which was highly expressed in TSCC, promoted EMT in tumor cells and accelerated their proliferation, invasion, and migration, which might provide a new theoretical basis for molecular targeted therapy of TSCC in the future.