Abstract 466: A potential pro-oncogenic role of SERPINB4 in melanoma

Abstract

Abstract Despite recent therapeutic advancements, melanoma remains one of the deadliest forms of skin cancer. Melanoma metastasis and recurrence is associated with the existence of heterogeneous cell populations within tumors that have the ability to both initiate metastatic programs and bypass immune recognition. Tumor cells achieve immune evasion by interfering with immune signaling to limit immune cell infiltration, allowing tumor cell proliferation and growth. SERPINB4 (Squamous Cell Carcinoma Antigen 2 or SCCA2), a serine protease inhibitor, has been shown to regulate the host immune response against tumor cells by inhibiting immune cell activity. Interestingly, certain cancer cell types have been reported to overexpress SERPINB4. However, the expression profile and the functional significance of SERPINB4 in melanoma is not known. In this study, employing ‘The Cancer Genome Atlas’ (TCGA), we found that SERPINB4 is overexpressed and significantly associated with lower overall survival in patients with melanoma. Next, employing a panel of human melanoma cell lines, we demonstrated that SERPINB4 is overexpressed in melanoma cells when compared to normal human melanocytes. In addition, CRISPR knockout of SERPINB4 in high-SERPINB4-expressing A375 melanoma cells resulted in a significant decrease in proliferation of melanoma cells in comparison to control cells. Conversely, forced overexpression of SERPINB4 in low-SERPINB4-expressing SK-MEL-2 and SK-MEL-28 melanoma cells significantly increased melanoma cell proliferation. Moreover, RT-qPCR analyses suggested that SERPINB4 overexpression significantly increased, while its knockout significantly decreased epithelial-mesenchymal transition (EMT) markers (N-cadherin, β-catenin, Snail and Zeb1) in melanoma cells. Additionally, SERPINB4 manipulation significantly modulated the expression of genes involved in antigen-presentation (MHC Class I molecules, HLA-A, -B, and -C) in melanoma cells. Taken together, our data suggested a potential oncogenic role of SERPINB4 in melanoma. Our study also suggested that SERPINB4 might be a promising therapeutic target for melanoma. Indeed, additional in vitro mechanistic and in vivo studies are needed to firmly establish the mechanism and therapeutic potential of SERPINB4 for melanoma management. Citation Format: Gagan Chhabra, Carl A. Shirley, Rachel K. Robarge, Hassan A. Rizvi, Mary A. Ndiaye, Nihal Ahmad. A potential pro-oncogenic role of SERPINB4 in melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 466.