Department of Experimental Therapeutics, MD Anderson Cancer Center, The University of Texas , Houston, TX , USA.
Department of Medicine, The Greenebaum Cancer Center, University of Maryland School of Medicine , Baltimore, MD , USA.
Front Oncol. 2015 Feb 16;5:21. doi: 10.3389/fonc.2015.00021. eCollection 2015.
Over the past decades, an emerging role of phosphatases in the pathogenesis of hematologic malignancies and solid tumors has been established. The tumor-suppressor protein phosphatase 2A (PP2A) belongs to the serine-threonine phosphatases family and accounts for the majority of serine-threonine phosphatase activity in eukaryotic cells. Numerous studies have shown that inhibition of PP2A expression and/or function may contribute to leukemogenesis in several hematological malignancies. Likewise, overexpression or aberrant expression of physiologic PP2A inhibitory molecules (e.g., SET and its associated SETBP1 and CIP2A) may turn off PP2A function and participate to leukemic progression. The discovery of PP2A as tumor suppressor has prompted the evaluation of the safety and the efficacy of new compounds, which can restore PP2A activity in leukemic cells. Although further studies are needed to better understand how PP2A acts in the intricate phosphatases/kinases cancer network, the results reviewed herein strongly support the development on new PP2A-activating drugs and the immediate introduction of those available into clinical protocols for leukemia patients refractory or resistant to current available therapies.
在过去的几十年中，磷酸酶在血液恶性肿瘤和实体瘤发病机制中的新作用已经确立。肿瘤抑制蛋白磷酸酶 2A（PP2A）属于丝氨酸/苏氨酸磷酸酶家族，占真核细胞中丝氨酸/苏氨酸磷酸酶活性的大部分。大量研究表明，抑制 PP2A 的表达和/或功能可能有助于几种血液恶性肿瘤的白血病发生。同样，生理 PP2A 抑制分子（例如 SET 及其相关 SETBP1 和 CIP2A）的过表达或异常表达可能会关闭 PP2A 功能并参与白血病进展。PP2A 作为肿瘤抑制因子的发现促使人们评估新化合物的安全性和疗效，这些新化合物可以恢复白血病细胞中的 PP2A 活性。尽管需要进一步研究以更好地了解 PP2A 在复杂的磷酸酶/激酶癌症网络中的作用，但本文综述的结果强烈支持开发新的 PP2A 激活药物，并立即将这些药物引入对现有疗法耐药或耐受的白血病患者的临床方案中。
