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

Nature Communications
Silvia PietrobonoBarbara Stecca

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.

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Citations

Apr 7, 2021·Critical Reviews in Biochemistry and Molecular Biology·Shuhui ChenLara K Mahal
Aug 28, 2021·Cells·Chiara De VellisBarbara Stecca

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Datasets Mentioned

BETA
GSE7553
GSE46517
GDS1375
GDS3966

Methods Mentioned

BETA
glycosylation
PCR
RNA-seq
bioluminescence
xenograft
immunoprecipitation assay
immunoprecipitation
xenografts
gene knockdown
scRNA-seq

Software Mentioned

MaxQuant
TFBIND
RTA
FlowJo
CytExpert
DAVID
Monocle3
M3Vision
Illumina
Image J

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