ArticleOncogenesis2021
PLEKHA5 regulates the survival and peritoneal dissemination of diffuse-type gastric carcinoma cells with Met gene amplification.
Article in Oncogenesis, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 21 citations in OpenAlex.
- A system-wide investigation into the phosphoregulatory network of TNIK and its cellular implications.Frontiers in bioinformatics · 2026Article
- Discovery, Optimization, and Anticancer Activity of Lipid-Competitive Pleckstrin Homology Domain-Containing Family A Inhibitors.Journal of medicinal chemistry · 2025Article
- Correlation between dyslipidaemia and gastric cancer: pathogenesis to prevention and treatment strategies.Lipids in health and disease · 2025Review
- TNFα activation of the PLEKHA5-FCRLA axis disturbs lipid metabolism, leading to the progression of cutaneous malignant melanoma.Lipids in health and disease · 2025Article
- Molecular mechanisms of metastatic peritoneal dissemination in gastric adenocarcinoma.Cancer metastasis reviews · 2025Review
- Cell Biology of Cancer Peritoneal Metastasis: Multiclonal Seeding and Peritoneal Tumor Microenvironment.Cancer science · 2025Review
- Single-cell transcriptomics and functional validation revealed PLEKHA5-L as a promoter of growth and migration in brain metastatic melanoma cells.Frontiers in oncology · 2025Article
- Multi-omics profiling reveals PLEKHA6 as a modulator of β-catenin signaling and therapeutic vulnerability in lung adenocarcinoma.American journal of cancer research · 2025Article
- Identifying potential drug targets for varicose veins through integration of GWAS and eQTL summary data.Frontiers in genetics · 2024Article
- [Lactate-induced up-regulation of PLEKHA4 promotes proliferation and apoptosis of human glioma cells].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2023Article
- Single cell profiling of γδ hepatosplenic T-cell lymphoma unravels tumor cell heterogeneity associated with disease progression.Cellular oncology (Dordrecht, Netherlands) · 2023Article
- Proximity Labeling Reveals Spatial Regulation of the Anaphase-Promoting Complex/Cyclosome by a Microtubule Adaptor.ACS chemical biology · 2022Article
- Review
- SHP2 as a Potential Therapeutic Target in Diffuse-Type Gastric Carcinoma Addicted to Receptor Tyrosine Kinase Signaling.Cancers · 2021Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Met gene amplification has been found in a subset of malignant carcinomas, including diffuse-type gastric carcinoma (DGC), which has a poor prognosis owing to rapid infiltrative invasion and frequent peritoneal dissemination. Met is considered a promising therapeutic target for DGC. However, DGC cells with Met gene amplification eventually acquire resistance to Met inhibitors. Therefore, identification of alternate targets that mediate Met signaling and confer malignant phenotypes is critical. In this study, we conducted a phosphoproteomic analysis of DGC cells possessing Met gene amplification and identified Pleckstrin Homology Domain Containing A5 (PLEKHA5) as a protein that is tyrosine-phosphorylated downstream of Met. Knockdown of PLEKHA5 selectively suppressed the growth of DGC cells with Met gene amplification by inducing apoptosis, even though they had acquired resistance to Met inhibitors. Moreover, PLEKHA5 silencing abrogated the malignant phenotypes of Met-addicted DGC cells, including peritoneal dissemination in vivo. Mechanistically, PLEKHA5 knockdown dysregulates glycolytic metabolism, leading to activation of the JNK pathway that promotes apoptosis. These results indicate that PLEKHA5 is a novel downstream effector of amplified Met and is required for the malignant progression of Met-addicted DGC.
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Registered trials
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.