Protein phosphatase 2A: a target for anticancer therapy.
Protein phosphatase 2A: a target for anticancer therapy.
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DOI：
10.1016/s1470-2045(12)70558-2
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发表时间：
2013-05
期刊：
影响因子：
--
通讯作者：
Neviani P
中科院分区：
文献类型：
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作者：
Perrotti D;Neviani P
蛋白磷酸酶2A（PP 2A）是哺乳动物细胞中主要的丝氨酸-苏氨酸磷酸酶之一，通过抵消大多数激酶驱动的细胞内信号转导途径来维持细胞内稳态。致癌激酶的不受限制的激活以及肿瘤抑制因子的抑制通常是癌症发展所必需的。由于PP 2A在许多实体癌和白血病中被发现基因改变或功能失活，因此它确实是一种真正的肿瘤抑制因子。例如，PP 2A的磷酸酶活性在慢性骨髓性白血病和以致癌激酶的异常活性为特征的其他恶性肿瘤中被抑制。值得注意的是，临床前研究表明，通过PP 2A活化药物（PAD，例如FTY 720）对PP 2A肿瘤抑制活性的药理学恢复有效地拮抗癌症的发展和进展。在此，我们系统地讨论了PP 2A作为一种可药物化的肿瘤抑制剂的重要性，鉴于可能将PAD引入抗癌治疗方案。
Protein phosphatase 2A (PP2A), one of the major serine-threonine phosphatases in mammalian cells, maintains cell homeostasis by counteracting most of the kinase-driven intracellular signaling pathways. Unrestrained activation of oncogenic kinases together with inhibition of tumor suppressors is frequently required for the development of cancer. Because it has been found genetically altered or functionally inactivated in many solid cancers and leukemias, PP2A is indeed a bona fide tumor suppressor. For example, the phosphatase activity of PP2A is suppressed in chronic myelogenous leukemia and other malignancies characterized by the aberrant activity of oncogenic kinases. Notably, preclinical studies indicate that pharmacologic restoration of PP2A tumor suppressor activity by PP2A activating drugs (PADs, e.g. FTY720) effectively antagonizes cancer development and progression. Herein, we systematically discuss the importance of PP2A as a druggable tumor suppressor in light of the possible introduction of PADs into anti-cancer therapeutic protocols.