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HS2ST1‐dependent signaling pathways determine breast cancer cell viability, matrix interactions, and invasive behavior

Abstract : Heparan sulfate proteoglycans (HSPGs) act as signaling co‐receptors by interaction of their sulfated glycosaminoglycan chains with numerous signaling molecules. In breast cancer, the function of heparan sulfate 2‐O‐sulfotransferase (HS2ST1), the enzyme mediating 2‐O‐sulfation of HS, is largely unknown. Hence, a comparative study on the functional consequences of HS2ST1 overexpression and siRNA knockdown was performed in the breast cancer cell lines MCF‐7 and MDA‐MB‐231. HS2ST1 overexpression inhibited Matrigel invasion, while its knockdown reversed the phenotype. Likewise, cell motility and adhesion to fibronectin and laminin were affected by altered HS2ST1 expression. Phosphokinase array screening revealed a general decrease in signaling via multiple pathways. Fluorescent ligand binding studies revealed altered binding of fibroblast growth factor 2 (FGF‐2) to HS2ST1‐expressing cells compared with control cells. HS2ST1‐overexpressing cells showed reduced MAPK signaling responses to FGF‐2, and altered expression of epidermal growth factor receptor (EGFR), E‐cadherin, Wnt‐7a, and Tcf4. The increased viability of HS2ST1‐depleted cells was reduced to control levels by pharmacological MAPK pathway inhibition. Moreover, MAPK inhibitors generated a phenocopy of the HS2ST1‐dependent delay in scratch wound
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https://hal.univ-reims.fr/hal-02934147
Contributor : Brigitte Perron <>
Submitted on : Wednesday, September 9, 2020 - 9:13:37 AM
Last modification on : Thursday, September 10, 2020 - 3:25:38 AM

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Archana Vijaya Kumar, Stéphane Brézillon, Valérie Untereiner, Ganesh Dhruvananda Sockalingum, Sampath Kumar Katakam, et al.. HS2ST1‐dependent signaling pathways determine breast cancer cell viability, matrix interactions, and invasive behavior. Cancer Science, Wiley Open Access, 2020, 111 (8), pp.2907-2922. ⟨10.1111/cas.14539⟩. ⟨hal-02934147⟩

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