(520.12) High-throughput Assay and In Vivo Screen Identify α-2,3-sialylation of CD98 by ST3GAL1 and ST3GAL2 as Essential to Melanoma Survival

Poster Board Number: A460

Shuhui Chen (New York University), Praveen Agrawal (Albert Einstein College of Medicine), Eva Hernando-Monge (NYU Grossman School of Medicine), Lara Mahal (University of Alberta, New York University)

Melanoma is an aggressive type of skin cancer that accounts for most skin cancer deaths, and the incidence of melanoma has increased rapidly over the past decades. Early-staged disease can be cured by surgery, however, a lack of curative treatments for patients with established melanoma metastasis results in significantly low survival rates. Thus, identification of key drivers in melanoma progression is essential to our understanding of melanoma biology. Glycosylation is a hallmark of cancer biology and altered glycosylation influences multiple facets of both tumor growth and progression. Herein, we utilized lectin microarrays to compare the glycomes of early transformation and melanoma progression. We found common glycan signatures, including an increase of α-2,3-sialosides, in both biological processes, and revealed glycans associated with site-specific metastasis. Tandem analysis of using an innovative functional in vivo growth screening of essential glycogenes identified the underlying sialyltransferases ST3GAL1 and ST3GAL2 as essential for melanoma growth. We confirmed upregulation of ST3GAL1 and ST3GAL2 in melanoma via examination of transcriptomic datasets and human tissue microarrays. Proteomic analysis identified CD98 as a candidate glycoprotein responsible for promoting melanoma proliferation. Our studies reveal glycans may act as molecular drivers that functionally contribute to melanoma biology and opens up novel paths to develop glycan-based therapeutics to treat melanoma patients.

Support or Funding Information

This project was supported by funding from DOD-CA171043 and also supported, in part, by funding from the Canada Excellence Research Chairs Program (L. K. M.).