Nox4 redox regulation of PTP1B contributes to the proliferation and migration of glioblastoma cells by modulating tyrosine phosphorylation of coronin-1C

Abstract

Collectively, these findings reveal that Nox4-mediated redox regulation of PTP1B serves as a modulator, in part through coronin-1C, of the growth and migration of glioblastoma cells, and provide new insight into the mechanistic aspect of glioblastoma malignancy.

Myc inhibition is effective against glioma and reveals a role for Myc in proficient mitosis

“…In contrast, U373MG cells display no such downregulation of SAE1 levels but Myc inhibition is instead associated with the phosphorylation of PTP1B, a modification described to trigger cell death during mitotic catastrophe30. The phosphatase PTP1B has been recently shown to exert antitumour effects in GBM32, however, it displays tumour-promoting effects in other cell types; opposing functions may be controlled by posttranslational modifications and substrate specificity. For example, PTP1B is negatively regulated by sumoylation upon entry into mitosis33, whereas its phosphorylation by Cdk1 and Plk1 during mitotic arrest promotes its activation and tumour suppressing activity30.…”

Redox-mediated signal transduction by cardiovascular Nox NADPH oxidases

“…Nox4 also contributes to insulin-induced ROS formation which by PTP1B oxidation facilitates insulin signaling [38,39]. Given the numerous targets of PTP1B, its Nox4-dependent oxidation modulates a spectrum of different cellular processes like the phosphorylation of the cytoskeletal protein coronin-1c [40] or the maintenance of endothelial barrier function. Here, PTP1B associates with β-catenin, p120-catenin und VE-cadherin.…”

Leptin and the brain: Influences on brain development, cognitive functioning and psychiatric disorders

“…In a similar fashion, the neuronspecific tyrosine phosphatase protein-tyrosine phosphatase 1B (PTP1B) knockout mice are overresponsive to the effects of exogenous leptin and show reduced adiposity and elevated energy expenditure with activity [48]. PTP1B may influence astrocyte migration and differentiation, mediating some of leptin's effects on neural development discussed below [49,50]. These data suggest that both SOCS3 and PTP1B are mediators that may lead to reduced LepRb signaling in obesity and influence brain functioning, although further mechanisms remain to be determined.…”