Emerging roles of PHLPP phosphatases in lung cancer

Xinhang Xia; Wenhu Pi; Meng Chen; Wei Wang; Danyang Cai; Xuequan Wang; Yanli Lan; Haihua Yang

doi:10.3389/fonc.2023.1216131

Emerging roles of PHLPP phosphatases in lung cancer

Front Oncol. 2023 Jul 27:13:1216131. doi: 10.3389/fonc.2023.1216131. eCollection 2023.

Authors

Xinhang Xia¹, Wenhu Pi¹, Meng Chen¹, Wei Wang¹, Danyang Cai¹, Xuequan Wang¹, Yanli Lan¹, Haihua Yang¹

Affiliation

¹ Key Laboratory of Radiation Oncology of Taizhou, Radiation Oncology Institute of Enze Medical Health Academy, Department of Radiation Oncology, Taizhou Hospital Affiliated to Wenzhou Medical University, Taizhou, Zhejiang, China.

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.

Keywords: PHLPP; lung cancer; phosphatase substrate; potential effect; therapeutic target.

Publication types

Review

Grants and funding

This work was supported in part by the Chinese National Science Foundation Projects (NSFC 81874221) and Basic Public Welfare Research Project of Zhejiang Province (LGF21H160027).