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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 signal-ing 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. This is an open access article under the terms of the Creat ive Commo ns Attri butio n-NonCo mmerc ial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
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https://hal.univ-reims.fr/hal-02986569
Contributor : Jean-Marc Ferez <>
Submitted on : Tuesday, November 17, 2020 - 11:25:35 AM
Last modification on : Thursday, December 3, 2020 - 3:12:33 AM

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Kumar et al CAS-111-2907 2020....
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Distributed under a Creative Commons Attribution - NonCommercial - NoDerivatives 4.0 International License

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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-02986569⟩

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