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

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

Abstracts of National Conference on Biological, Biochemical, Biomedical, Bioenergy, and Environmental Biotechnology

This book contains the abstracts of the papers presented at the National Conference on Biological, Biochemical, Biomedical, Bioenergy, and Environmental Biotechnology (NCB4EBT-2021) Organized by the Department of Biotechnology, National Institute of Technology Warangal, India held on 29–30 January 2021. This conference is the first of its kind organized by NIT-W which covered an array of interesting topics in biotechnology. This makes it a bit special as it brings together researchers from different disciplines of biotechnology, which in turn will also open new research and cooperation fields for them. Conference Title: National Conference on Biological, Biochemical, Biomedical, Bioenergy, and Environmental BiotechnologyConference Acronym: NCB4EBT-2021Conference Date: 29–30 January 2021Conference Location: Online (Virtual Mode)Conference Organizer: Department of Biotechnology, National Institute of Technology Warangal, Indi

A Meta-analysis of Gene Expression Signatures of Blood Pressure and Hypertension

10.1371/journal.pgen.1005035PLoS Genetics113e100503