Abstract
Abstract Melanoma is the deadliest form of skin cancer; while early detection affords patients a 5-year survival rate greater than 90 percent, survival for metastatic patients is poor. Metastatic dissemination is reliant on melanoma’s ability to escape immune surveillance and migrate to distant organs. These processes are heavily influenced by cell surface proteins, which themselves can be regulated by post-translational modifications (PTM) like protein glycosylation. An understudied glycosylation that may affect immune evasion and cancer progression is polysialylation (polySia). Here, a long-chained polymer of sialic acid moieties is formed by the polysialyltransferases ST8SIA2 and ST8SIA4. In silico analysis suggests that compared to normal skin, primary cutaneous melanoma has elevated expression of both ST8SIA2 and ST8SIA4. Interestingly, although ST8SIA4 is upregulated in metastatic samples, its expression is associated with increased survival. Further analysis revealed a positive correlation between CD8+ T cell infiltrates and ST8SIA4 expression. Furthermore, analysis of ST8SIA2 expression shows an inverse correlation with survival and T Cell CD8+ cells infiltration, suggesting ST8SIA2 and -4 differentially regulate the tumor immune microenvironment. One potential polySia modified cell surface protein, mediating these effects is Cell Adhesion Molecule 1 (CADM1). CADM1 is a target of ST8SIA2 and may also be modified by ST8SIA4. Loss of CADM1 increases the invasive properties of melanoma cells and our recent point mutational analysis reveals that the adhesive function of CADM1 might be regulated by polySia at Asp 113. In addition to its role in cancer migration and invasiveness, CADM1 expression may also affect the tumor immune environment. Further investigations are needed to untangle the complex relationship between PolySia modification and melanoma immune evasion and metastasis. Citation Format: Amirali Amirfallah, Kayla Gallant, Maria Cavallo, Zongguan Huang, Edward Hartsough. The role of ST8SIA2 & ST8SIA4 in melanoma progression and metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1398.
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