ArticleOncotarget2018
PHLDA2 is a key oncogene-induced negative feedback inhibitor of EGFR/ErbB2 signaling via interference with AKT signaling.
Article in Oncotarget, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 33 citations in OpenAlex.
- Genes Associated with Apoptosis in an Experimental Breast Cancer Model.International journal of molecular sciences · 2025Article
- PHLDA2 in cancer: From molecular mechanisms to therapeutic opportunities.The Journal of pharmacology and experimental therapeutics · 2025Review
- Multiomics Analysis of the PHLDA Gene Family in Different Cancers and Their Clinical Prognostic Value.Current issues in molecular biology · 2024Article
- FGF10 mitigates doxorubicin-induced myocardial toxicity in mice via activation of FGFR2b/PHLDA1/AKT axis.Acta pharmacologica Sinica · 2023Article
- A novel stratification framework based on anoikis-related genes for predicting the prognosis in patients with osteosarcoma.Frontiers in immunology · 2023Article
- Increased copy number of imprinted genes in the chromosomal region 20q11-q13.32 is associated with resistance to antitumor agents in cancer cell lines.Clinical epigenetics · 2022Article
- Qualitative differences in disease-associated MEK mutants reveal molecular signatures and aberrant signaling-crosstalk in cancer.Nature communications · 2022Article
- AnEuropean journal of breast health · 2022Article
- Cancer-Associated Fibroblasts and Squamous Epithelial Cells Constitute a Unique Microenvironment in a Mouse Model of Inflammation-Induced Colon Cancer.Frontiers in oncology · 2022Article
- A genome-wide atlas of co-essential modules assigns function to uncharacterized genes.Nature genetics · 2021Article
- The expression patterns and prognostic significance of pleckstrin homology-like domain family A (PHLDA) in lung cancer and malignant mesothelioma.Journal of thoracic disease · 2021Article
- PHLD Class Proteins: A Family of New Players in the p53 Network.International journal of molecular sciences · 2020Review
- Upregulation of miR-214 Induced Radioresistance of Osteosarcoma by Targeting PHLDA2 via PI3K/Akt Signaling.Frontiers in oncology · 2019Article
- PHLDA1, another PHLDA family protein that inhibits Akt.Cancer science · 2018Article
- Molecular pathogenesis of pancreatic ductal adenocarcinoma: Impact of passenger strand of pre-miR-148a on gene regulation.Cancer science · 2018Article
- Transcriptionally inducible Pleckstrin homology-like domain, family A, member 1, attenuates ErbB receptor activity by inhibiting receptor oligomerization.The Journal of biological chemistry · 2018Article
- Interleukin-1 beta transactivates epidermal growth factor receptor via the CXCL1-CXCR2 axis in oral cancer.Oncotarget · 2015Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pleckstrin homology-like domain family A member 2 (PHLDA2) is located within the tumor suppressor region of 11p15, and its expression is suppressed in several malignant tumor types. We recently identified PHLDA2 as a robustly induced, novel downstream target of oncogenic EGFR/ErbB2 signaling. In an immunohistochemical study, we find that PHLDA2 protein expression correlates positively with AKT activation in human lung cancers corroborating our data that PHLDA2 is induced upon oncogenic activation and might serve as a biomarker for AKT pathway activation. We show that PHLDA2 overexpression inhibits AKT phosphorylation while decreased PHLDA2 expression increases AKT activity. We further find that PHLDA2 competes with the PH domain of AKT for binding of membrane lipids, thereby directly inhibiting AKT translocation to the cellular membrane and subsequent activation. Indeed, PHLDA2 overexpression suppresses anchorage-independent cell growth and decreased PHLDA2 expression results in increased cell proliferation and reduced sensitivity to targeted agents of EGFR/ErbB2-driven cancers demonstrating functional relevance for this interaction. In summary, our studies demonstrate that PHLDA2 is strongly regulated by EGFR/ErbB2 signaling and inhibits cell proliferation via repressing AKT activation in lung cancers in a negative feedback loop. We highlight a novel action for PHLDA2 as a potential biomarker for AKT pathway activation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.