Abstract LB013: Integrated in vivo functional screens and multi-omics analyses identify alpha-2,3-sialylation as essential for melanoma survival

Abstract

Abstract Glycosylation is a hallmark of cancer biology, and altered glycosylation influences multiple facets of melanoma growth and progression. To identify glycosyltransferases, glycans, and glycoproteins essential for melanoma survival, we conducted an in vivo growth screen with a pooled shRNA library of glycosyltransferases, lectin microarray profiling of benign nevi and melanoma patient samples, and mass spectrometry-based glycoproteomics. We found that alpha-2,3 sialyltransferases ST3GAL1 and ST3GAL2 and corresponding alpha-2,3-linked sialosides are upregulated in melanoma compared to nevi and are essential for melanoma growth in vivo and in vitro. Glycoproteomics revealed that glycoprotein targets of ST3GAL1 and ST3GAL2 are enriched in transmembrane proteins involved in growth signaling, including the amino acid transporter Solute Carrier Family 3 Member 2 (SLC3A2/CD98hc). CD98hc suppression mimicked the effect of ST3GAL1 and ST3GAL2 silencing, inhibiting melanoma cell proliferation. We found that both CD98hc protein stability and its pro-survival effect in melanoma are dependent upon alpha–2,3 sialylation mediated by ST3GAL1 and ST3GAL2. In summary, our studies reveal that alpha-2,3-sialosides functionally contribute to melanoma maintenance, supporting ST3GAL1 and ST3GAL2 as novel therapeutic targets in these tumors. Citation Format: Praveen Agrawal. Integrated in vivo functional screens and multi-omics analyses identify alpha-2,3-sialylation as essential for melanoma survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB013.