蛋白磷酸酶 2A（PP2A）在脑肿瘤中的关键作用。

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

机构信息

Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres, 31-98166 Messina, Italy.

Istituto Oncologico del Mediterraneo, Via Penninazzo 7, 95029 Viagrande, Italy.

出版信息

Int J Mol Sci. 2022 Dec 11;23(24):15717. doi: 10.3390/ijms232415717.

DOI:10.3390/ijms232415717

PMID:36555359

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9779694/

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.

摘要

蛋白磷酸酶 2A（PP2A）是一种高度复杂的 Ser/Thr 磷酸酶，调节许多细胞过程。PP2A 在几种人类疾病中失调，包括肿瘤病理学；有趣的是，PP2A 似乎对控制细胞生长至关重要，并且可能与癌症的发展有关。PP2A 作为肿瘤抑制因子的作用已被广泛研究和综述。为了利用组合 PP2A 抑制和放射治疗的潜在临床效用，开发新型高度特异性的 PP2A 抑制剂至关重要。在这篇综述中，分析了现有关于 PP2A 在脑肿瘤，特别是在神经胶质瘤和神经胶质瘤（GBM）中的作用的文献。有趣的是，该综述重点关注了 PP2A 抑制剂的作用，重点关注 CIP2A 抑制，因为 CIP2A 通过刺激细胞更新存活、细胞增殖、逃避衰老和抑制细胞凋亡来参与肿瘤细胞生长。该综述提出 CIP2A 抑制作为肿瘤学靶向治疗的一种有前途的策略。