Abstract
This research aimed to investigate the expression and function of FAM83A in the proliferation and metastasis in head and neck squamous cell carcinoma (HNSCC). FAM83A mRNA and protein expressions in HNSCC were detected in 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 cell growth and metastasis in vitro and the relationship between FAM83A and epithelial-mesenchymal transition (EMT). Furthermore, two models of xenograft tumors in nude mice were used to assess the tumorigenicity and metastasis ability of FAM83A in vivo. In the present study, overexpression of FAM83A in HNSCC samples was significantly associated with tumor size, lymph node status and clinical tumor stages. 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 the function of FAM83A. Also, the FAM83A knockdown could suppress tumor growth and distant metastasis in the xenograft animal models of HNSCC. In conclusion, this study identifies FAM83A as an oncogene of HNSCC. This study provides new insights into the molecular pathways that contribute to EMT in HNSCC. We revealed a previously unknown FAM83A-Wnt–β-catenin signaling axis involved in the EMT of HNSCC. There may be a potential bi-directional signaling loop between FAM83A and Wnt/β-catenin signaling pathway in HNSCC.
Highlights
In recent years, head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers worldwide, with more than 350,000 cancer-related deaths per year even though combined and multidisciplinary therapy has greatly advanced [1, 2]
Previous studies have highlighted that the up-regulated FAM83A often functions as an oncogenic gene in tumorigenesis
Immunohistochemistry in human HNSCC microarrays showed aberrant overexpression of FAM83A in a large number of patients compared with adjacent normal tissues
Summary
Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers worldwide, with more than 350,000 cancer-related deaths per year even though combined and multidisciplinary therapy has greatly advanced [1, 2]. Prior studies have suggested that FAM83A is abnormally expressed and involved in the progression of multiple human cancers [4,5,6,7,8,9,10,11,12,13]. Ji et al J Transl Med (2021) 19:423 be a diagnostic and prognostic marker of non-small cell lung cancer and is closely related to tumor histology and signal transduction [14, 15]. FAM83A/PD-L1 coexpression correlates with poor prognosis in lung adenocarcinoma, and FAM83A drives PD-L1 expression via ERK signaling, causing tumor immune escape [13]
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