S-glutathionylation is one of the major oxidative modifications mediated by reactive oxygen species under metabolic stress. This oxidative modification modulates various biological processes such as cell invasion, apoptosis, and cell migration. Cell migration is an important event in wound healing and cancer metastasis. However, the underlying mechanisms on how glutathionylation is involved in signaling pathways to modulate cell migration are not well understood. Despite the known relationship between redox proteins and cell migration, the identity of specific redox-regulated cysteines is limited.<br/>This work has used proteomic data and Cytoscape bioinformatic tool to narrow down 38 candidate proteins that may alter migration upon glutathionylation. Out of these candidates, we investigated nine proteins by wound healing assay under low glucose conditions. Wild type and cysteine to serine mutants were transfected to MDA-MB 231 cells and wound healing assays were conducted under 25 mM and 5 mM glucose. Interestingly, three proteins, NISCH, ARHGEF7, and PP2Calpha resulted in increased migration under low glucose, implying that glutathionylation of specific cysteines promotes cell migration. Moreover, we observed that DAAO (D amino acid oxidase) transfected MCF7 cells increase cell migration in a D-alanine dose-dependent manner under low glucose. These findings may direct to identify new protein targets and their specific redox cysteines involved in migration.

Metabolic stress-induced glutathionylation promotes cancer cell migration

ACS Spring Meeting 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.