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Heparan sulfate proteoglycan modulation of Wnt5A signal transduction in metastatic melanoma cells.


ABSTRACT: Heparan sulfate proteoglycans (HSPGs) are important modulators for optimizing signal transduction of many pathways, including the Wnt pathways. We demonstrate that HSPG glycosaminoglycan levels increased with increasing metastatic potential of melanoma cells. Previous studies have demonstrated that Wnt5A increases the invasiveness of melanoma cells. We further demonstrate that HSPGs potentiate Wnt5A signaling, since enzymatic removal of the HSPG backbone resulted in a decrease in cellular Wnt5A levels, an increase in secreted Wnt5A in cell media, a decrease in downstream signaling, and ultimately, a decrease in invasiveness. Specifically, syndecan 1 and syndecan 4 expression correlated to Wnt5A expression and melanoma malignancy. Knockdown of syndecan 1 or 4 caused decreases in cell invasion, which could be restored by treating the cells with recombinant Wnt5A. These data indicate that syndecan 1 and 4 correlate to increased metastatic potential in melanoma patients and are an important component of the Wnt5A autocrine signaling loop, the activation of which leads to increased metastasis of melanoma.

SUBMITTER: O'Connell MP 

PROVIDER: S-EPMC2781415 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

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Heparan sulfate proteoglycan modulation of Wnt5A signal transduction in metastatic melanoma cells.

O'Connell Michael P MP   O'Connell Michael P MP   Fiori Jennifer L JL   Kershner Emily K EK   Frank Brittany P BP   Indig Fred E FE   Taub Dennis D DD   Hoek Keith S KS   Weeraratna Ashani T AT  

The Journal of biological chemistry 20090820 42


Heparan sulfate proteoglycans (HSPGs) are important modulators for optimizing signal transduction of many pathways, including the Wnt pathways. We demonstrate that HSPG glycosaminoglycan levels increased with increasing metastatic potential of melanoma cells. Previous studies have demonstrated that Wnt5A increases the invasiveness of melanoma cells. We further demonstrate that HSPGs potentiate Wnt5A signaling, since enzymatic removal of the HSPG backbone resulted in a decrease in cellular Wnt5A  ...[more]

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