Unraveling the complexity: A comprehensive analysis of the PP2A in cancer and its potential for novel targeted therapies.

IF 2 4区医学 Q3 ONCOLOGY

Neoplasma Pub Date : 2023-08-01 DOI:10.4149/neo_2023_230806N411

Danica Ivovič, Pavlína Kabelíková, Dana Jurkovičová

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Abstract

Protein phosphatase 2A (PP2A) is a major serine/threonine phosphatase considered a potent tumor suppressor that critically regulates diverse cellular processes, including cell cycle progression, apoptosis, or DNA repair. PP2A is typically downregulated in cancers but mechanisms for its inactivation in human cancers are poorly understood. PP2A represents a family of more than 60 phosphatases. According to cellular context, each heterotrimeric PP2A holoenzyme exerts a unique role in cancer, and PP2A isoforms can act either as tumor suppressors or as promoters. Due to wide structural diversity, PP2A has been considered undruggable. However, increasing knowledge predisposes PP2A diversity to therapeutical targeting for the treatment of a broad range of cancer pathologies, including drug resistance or cloaking immune surveillance. In this review, we discuss the regulatory role of PP2A in cancer, its regulation by microRNA and hypoxia, its contribution to therapy resistance development, and the therapeutic potential of direct and indirect targeting, or combinatory administration with other anti-cancer drugs to improve cancer treatment outcomes.

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解开复杂性：对癌症中PP2A及其新靶向治疗潜力的全面分析。

蛋白磷酸酶2A（PP2A）是一种主要的丝氨酸/苏氨酸磷酸酶，被认为是一种有效的肿瘤抑制因子，对多种细胞过程进行关键调控，包括细胞周期进展、细胞凋亡或DNA修复。PP2A在癌症中通常下调，但其在人类癌症中失活的机制尚不清楚。PP2A代表一个由60多种磷酸酶组成的家族。根据细胞背景，每种异源三聚体PP2A全酶在癌症中发挥独特的作用，PP2A亚型可以作为肿瘤抑制剂或启动子。由于广泛的结构多样性，PP2A被认为是不可加固的。然而，知识的增加使PP2A的多样性倾向于治疗靶向性，用于治疗广泛的癌症病理，包括耐药性或隐形免疫监测。在这篇综述中，我们讨论了PP2A在癌症中的调节作用，其通过微小RNA和缺氧的调节，其对治疗耐药性发展的贡献，以及直接和间接靶向或与其他抗癌药物联合用药以改善癌症治疗结果的治疗潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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