Overexpression of FAM83A Promotes Proliferation and Metastasis Via Activating Wnt/β-catenin Signaling Pathway in Head Neck Squamous Cell Carcinoma

Abstract Purpose:This research aimed to investigate FAM83A expression in head and neck squamous cell carcinoma (HNSCC) and its function in the proliferation and metastasis. Materials and Methods: FAM83A mRNA and protein expression in HNSCC was detected via TCGA database, primary HNSCC samples, and cell lines. The associations between FAM83A expression and clinicopathologic variables were evaluated through tissue microarrays. Besides, FAM83A knockdown and overexpression cell lines were constructed to assess its biological function including cell growth and metastasis in vitro and the relationship between FAM83A and epithelial-mesenchymal transition (EMT) was explored. Furthermore, two models of xenograft tumors in nude mice were used to assess the tumorigenicity and metastasis ability of FAM83A in vivo. Results: In the present study, we discovered the FAM83A expression was overexpressed in the HNSCC samples and was significantly associated with tumor size, lymph node status, and pathological grades. Mechanically, FAM83A could promote HNSCC cell growth and metastasis by inducing EMT via activating Wnt/β-catenin signaling pathway. Rescue experiment demonstrated the inhibition of β-catenin could counteract FAM83A function and there is a bi-directional signaling loop between FAM83A and Wnt/β-catenin signaling pathways. Also, the FAM83A knockdown could suppress tumor growth and distant metastasis in HNSCC xenograft animal models. Conclusions: Taken together, we demonstrated that FAM83A is upregulated in HNSCC and it could promote cell growth and metastasis via activating Wnt/β-catenin pathway in HNSCC, which may provide a novel therapeutic target in HNSCC treatment.