ArticleOncogene2018
PHLPP1 mediates melanoma metastasis suppression through repressing AKT2 activation.
Article in Oncogene, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 38 citations in OpenAlex.
- PHLPP is neither a Phosphatase nor a Tumor Suppressor.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
- Comprehensive transcriptomic characterization of two melanoma cell lines with acquired dual resistance to BRAF and MEK inhibitors.Scientific reports · 2026Article
- Targeting one-carbon metabolic vulnerabilities of metastasis with therapeutic potential.bioRxiv : the preprint server for biology · 2026Article
- Article
- Early Onset Colorectal Cancer: Molecular Underpinnings Accelerating Occurrence.Cellular and molecular gastroenterology and hepatology · 2025Review
- TRIM-endous functional network of tripartite motif 29 (TRIM29) in cancer progression and beyond.Cancer metastasis reviews · 2024Review
- MicroRNA-650 promotes melanoma metastasis via targeting inhibitor of growth family member 4.Heliyon · 2024Article
- Development of Personalized Strategies for Precisely Battling Malignant Melanoma.International journal of molecular sciences · 2024Review
- Logic-based modeling and drug repurposing for the prediction of novel therapeutic targets and combination regimens against E2F1-driven melanoma progression.BMC chemistry · 2023Article
- AKT2 Loss Impairs BRAF-Mutant Melanoma Metastasis.Cancers · 2023Article
- SKP2 Contributes to AKT Activation by Ubiquitination Degradation of PHLPP1, Impedes Autophagy, and Facilitates the Survival of Thyroid Carcinoma.Molecules and cells · 2023Article
- PTEN phosphatase inhibits metastasis by negatively regulating the Entpd5/IGF1R pathway through ATF6.iScience · 2023Article
- AKT1 Is Required for a Complete Palbociclib-Induced Senescence Phenotype in BRAF-V600E-Driven Human Melanoma.Cancers · 2022Article
- Genomic and Transcriptomic Underpinnings of Melanoma Genesis, Progression, and Metastasis.Cancers · 2021Review
- Emerging roles of PHLPP phosphatases in metabolism.BMB reports · 2021Review
- PERK mediates resistance to BRAF inhibition in melanoma with impaired PTEN.NPJ precision oncology · 2021Article
- The Multifaceted Role of CMA in Glioma: Enemy or Ally?International journal of molecular sciences · 2021Review
- Article
- PHLPP2 as a novel metastatic and prognostic biomarker in non-small cell lung cancer patients.Thoracic cancer · 2019Article
- Silencing of TRIM11 suppresses the tumorigenicity of chordoma cells through improving the activity of PHLPP1/AKT.Cancer cell international · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
PI3K/AKT pathway activation is thought to be a driving force in metastatic melanomas. Members of the pleckstrin homology (PH) domain leucine-rich repeat protein Ser/Thr specific phosphatase family (PHLPP1 and PHLPP2) can regulate AKT activation. By dephosphorylating specific serine residues in the hydrophobic motif, PHLPP1 and PHLPP2 restrain AKT signalings, thereby regulating cell proliferation and survival. We here show that PHLPP1 expression was significantly downregulated or lost and correlated with metastatic potential in melanoma. Forcing expression of either PHLPP1 or PHLPP2 in melanoma cells inhibited cell proliferation, migration, and colony formation in soft agar; but PHLPP1 had the most profound inhibitory effect on metastasis. Moreover, expression of PH mutant forms of PHLPP1 continued to inhibit metastasis, whereas a phosphatase-dead C-terminal mutant did not. The introduction of activated PHLPP1-specific targets AKT2 or AKT3 also promoted melanoma metastasis, while the non-PHLPP1 target AKT1 did not. AKT2 and AKT3 could even rescue the PHLPP1-mediated inhibition of metastasis. An AKT inhibitor blocked the activity of AKT2 and inhibited AKT2-mediated tumor growth and metastasis in a preclinical mouse model. Our data demonstrate that PHLPP1 functions as a metastasis suppressor through its phosphatase activity, and suggest that PHLPP1 represents a novel diagnostic and therapeutic marker for metastatic melanoma.
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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.