ST3GAL1 is a target of the SOX2-GLI1 transcriptional complex and promotes melanoma metastasis through AXL

Silvia Pietrobono, Giulia Anichini, Cesare Sala, Fabrizio Manetti, Luciana L. Almada, Sara Pepe, Ryan M. Carr, Brooke D. Paradise, Jann N. Sarkaria, Jaime I. Davila, Lorenzo Tofani, Ilaria Battisti, Giorgio Arrigoni, Li Ying, Cheng Zhang, Hu Li, Alexander Meves, Martin E. Fernandez-Zapico, Barbara Stecca

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Understanding the molecular events controlling melanoma progression is of paramount importance for the development of alternative treatment options for this devastating disease. Here we report a mechanism regulated by the oncogenic SOX2-GLI1 transcriptional complex driving melanoma invasion through the induction of the sialyltransferase ST3GAL1. Using in vitro and in vivo studies, we demonstrate that ST3GAL1 drives melanoma metastasis. Silencing of this enzyme suppresses melanoma invasion and significantly reduces the ability of aggressive melanoma cells to enter the blood stream, colonize distal organs, seed and survive in the metastatic environment. Analysis of glycosylated proteins reveals that the receptor tyrosine kinase AXL is a major effector of ST3GAL1 pro-invasive function. ST3GAL1 induces AXL dimerization and activation that, in turn, promotes melanoma invasion. Our data support a key role of the ST3GAL1-AXL axis as driver of melanoma metastasis, and highlight the therapeutic potential of targeting this axis to treat metastatic melanoma.

Original languageEnglish (US)
Article number5865
JournalNature communications
Volume11
Issue number1
DOIs
StatePublished - Dec 2020

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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