Arginine deprivation affects glioblastoma cell adhesion, invasiveness and actin cytoskeleton organization by impairment of β-actin arginylation.

Abstract

A deficit of exogenous arginine affects growth and viability of numerous cancer cells. Although arginine deprivation-based strategy is currently undergoing clinical trials, molecular mechanisms of tumor cells' response to arginine deprivation are not yet elucidated. We have examined effects of arginine starvation on cell motility, adhesion and invasiveness as well as on actin cytoskeleton organization of human glioblastoma cells. We observed for the first time that arginine, but not lysine, starvation affected cell morphology, significantly inhibited their motility and invasiveness, and impaired adhesion. No effects on glia cells were observed. Also, arginine deprivation in glioblastoma evoked specific changes in actin assembly, decreased β-actin filament content, and affected its N-terminal arginylation. We suggest that alterations in organization of β-actin resulted from a decrease of its arginylation could be responsible for the observed effects of arginine deprivation on cell invasiveness and migration. Our data indicate that arginine deprivation-based treatment strategies could inhibit, at least transiently, the invasion process of highly malignant brain tumors and may have a potential for combination therapy to extend overall patient survival.