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Integrated in vivo functional screens and multi-omics analyses identify α-2,3-sialylation as essential for melanoma maintenance.
Agrawal, Praveen; Chen, Shuhui; de Pablos, Ana; Jame-Chenarboo, Faezeh; Miera Saenz de Vega, Eleazar; Darvishian, Farbod; Osman, Iman; Lujambio, Amaia; Mahal, Lara K; Hernando, Eva.
Afiliación
  • Agrawal P; Department of Pathology, NYU Grossman School of Medicine, New York.
  • Chen S; Interdisciplinary Melanoma Cooperative Group, Perlmutter Cancer Center, NYU Langone Health.
  • de Pablos A; Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York.
  • Jame-Chenarboo F; Department of Chemistry, New York University.
  • Miera Saenz de Vega E; Department of Pathology, NYU Grossman School of Medicine, New York.
  • Darvishian F; Interdisciplinary Melanoma Cooperative Group, Perlmutter Cancer Center, NYU Langone Health.
  • Osman I; Centro Nacional de Investigaciones Oncologicas (CNIO), Madrid, Spain.
  • Lujambio A; Department of Chemistry, University of Alberta, Edmonton, Canada.
  • Mahal LK; Department of Dermatology, NYU Grossman School of Medicine, New York.
  • Hernando E; Department of Pathology, NYU Grossman School of Medicine, New York.
bioRxiv ; 2024 Mar 12.
Article en En | MEDLINE | ID: mdl-38559078
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 maintenance, 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 α-2,3 sialyltransferases ST3GAL1 and ST3GAL2 and corresponding α-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 α-2,3 sialylation mediated by ST3GAL1 and ST3GAL2. In summary, our studies reveal that α-2,3-sialosides functionally contribute to melanoma maintenance, supporting ST3GAL1 and ST3GAL2 as novel therapeutic targets in these tumors.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos