TY  - JOUR
AB  - 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 repair. In conclusion, HS2ST1 modulation of breast cancer cell invasiveness is a compound effect of altered E-cadherin and EGFR expression, leading to altered signaling via MAPK and additional pathways.
AU  - Kumar, Archana Vijaya
AU  - Brézillon, Stéphane
AU  - Untereiner, Valérie
AU  - Sockalingum, Ganesh Dhruvananda
AU  - Katakam, Sampath Kumar
AU  - Mohamed, Hossam Taha
AU  - Kemper, Björn
AU  - Greve, Burkhard
AU  - Mohr, Benedikt
AU  - Ibrahim, Sherif
AU  - Goycoolea, Francisco Martin
AU  - Kiesel, Ludwig
AU  - Pavão, Mauro S. G.
AU  - Motta, Juliana M.
AU  - Götte, Martin
DA  - 2020-06-23
DO  - 10.17879/43069483491
KW  - 2-O-sulfotransferase
KW  - breast cancer
KW  - heparan sulfate
KW  - MAPK signaling pathway
KW  - proteoglycan
LA  - eng
N1  - Cancer Science 111 (2020) 8, 2907-2922
N1  - Finanziert über die DEAL-Vereinbarung mit Wiley 2019-2022.
PY  - 2020-06-23
TI  - HS2ST1-dependent signaling pathways determine breast cancer cell viability, matrix interactions, and invasive behavior
UR  - https://nbn-resolving.org/urn:nbn:de:hbz:6-63059650863
Y2  - 2024-11-22T03:07:54
ER  -