Emerging roles of PHLPP phosphatases in lung cancer

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...

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Published inFrontiers in oncology Vol. 13; p. 1216131
Main Authors Xia, Xinhang, Pi, Wenhu, Chen, Meng, Wang, Wei, Cai, Danyang, Wang, Xuequan, Lan, Yanli, Yang, Haihua
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 27.07.2023
Subjects
lung cancer
Oncology
PHLPP
phosphatase substrate
potential effect
therapeutic target
lung cancer
phosphatase substrate
therapeutic target
PHLPP
potential effect
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Summary: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.
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These authors have contributed equally to this work and share first authorship
Reviewed by: Xiaoling Zhang, Jilin University, China; Aimin Jiang, The First Affiliated Hospital of Xi’an Jiaotong University, China
Edited by: Mehdi Pirooznia, Johnson & Johnson, United States
ISSN:2234-943X
2234-943X
DOI:10.3389/fonc.2023.1216131