The Pivotal Role of Protein Phosphatase 2A (PP2A) in Brain Tumors

Abstract

Protein phosphatase 2A (PP2A) is a highly complex heterotrimeric Ser/Thr phosphatase that regulates many cellular processes. PP2A is dysregulated in several human diseases, including oncological pathology; interestingly, PP2A appears to be essential for controlling cell growth and may be involved in cancer development. The role of PP2A as a tumor suppressor has been extensively studied and reviewed. To leverage the potential clinical utility of combination PP2A inhibition and radiotherapy treatment, it is vital that novel highly specific PP2A inhibitors be developed. In this review, the existing literature on the role of PP2A in brain tumors, especially in gliomas and glioblastoma (GBM), was analyzed. Interestingly, the review focused on the role of PP2A inhibitors, focusing on CIP2A inhibition, as CIP2A participated in tumor cell growth by stimulating cell-renewal survival, cellular proliferation, evasion of senescence and inhibition of apoptosis. This review suggested CIP2A inhibition as a promising strategy in oncology target therapy.

Unlocking the potential ofmiR-19bin the regulation of temozolomide response in glioblastoma patients via targeting PPP2R5E, a subunit of the protein phosphatase 2A complex

“…The mechanism of DNA damage elicited by PPP2R5E reactivation is unknown. PP2A induction is associated with enhanced senescence in melanoma (34), KRAS-driven lung cancer (35) and GBM (36), but the underlying mechanism is unknown. Phosphoproteomics and transcriptomics analysis revealed a role of PP2A holoenzyme in metabolic enzyme induction and NRF2-mediated oxidative stress response pathways (37), which may lead to elevated ROS production, and DNA damage.…”