PDF(Pubmed)
Abstract：
Pleckstrin homologous domain leucine-rich repeating protein phosphatases (PHLPPs) were originally identified as protein kinase B (Akt) kinase hydrophobic motif specific phosphatases to maintain the cellular homeostasis. With the continuous expansion of PHLPPs research, imbalanced-PHLPPs were mainly found as a tumor suppressor gene of a variety of solid tumors. In this review, we simply described the history and structures of PHLPPs and summarized the recent achievements in emerging roles of PHLPPs in lung cancer by 1) the signaling pathways affected by PHLPPs including Phosphoinositide 3-kinase (PI3K)/AKT, RAS/RAF/mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) and Protein kinase C (PKC) signaling cascades. 2) function of PHLPPs regulatory factor USP46 and miR-190/miR-215, 3) the potential roles of PHLPPs in disease prognosis, Epidermal growth factor receptors (EGFR)- tyrosine kinase inhibitor (TKI) resistance and DNA damage, 4) and the possible function of PHLPPs in radiotherapy, ferroptosis and inflammation response. Therefore, PHLPPs can be considered as either biomarker or prognostic marker for lung cancer treatment.
摘要：
Pleckstrin同源域富含亮氨酸的重复蛋白磷酸酶（PHLPP）最初被鉴定为蛋白激酶B（Akt）激酶疏水性基序特异性磷酸酶，以维持细胞稳态。随着PHLPPs研究的不断扩大,不平衡-PHLPPs主要作为多种实体瘤的抑癌基因。在这次审查中,我们简单描述了PHLPPs的历史和结构，并通过以下方法总结了PHLPPs在肺癌中新兴作用的最新成就：1）受PHLPPs影响的信号通路，包括磷酸肌醇3激酶（PI3K）/AKT，RAS/RAF/丝裂原活化蛋白激酶(MEK)/细胞外信号调节激酶(ERK)和蛋白激酶C(PKC)信号级联。2)PHLPPs调控因子USP46和miR-190/miR-215的功能,3)PHLPPs在疾病预后中的潜在作用,表皮生长因子受体（EGFR）-酪氨酸激酶抑制剂（TKI）抗性和DNA损伤，4）和PHLPPs在放疗中的可能功能，铁性凋亡和炎症反应。因此,PHLPP可以被认为是肺癌治疗的生物标志物或预后标志物。
