ArticleNature communications2018
Deregulated PP1α phosphatase activity towards MAPK activation is antagonized by a tumor suppressive failsafe mechanism.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 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.
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Who cites it
27 citing papers in PubMed, 63 citations in OpenAlex.
- Decoding SR protein regulation: kinases, phosphatases, and therapeutic targeting strategies.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- NY-ESO-1 facilitates anoikis resistance and tumor metastasis by hijacking deubiquitinase OTUB1 to stabilize PP1α.Cell death & disease · 2025Article
- Development of a PPP1R14B-associated immune prognostic model for hepatocellular carcinoma.European journal of medical research · 2025Article
- Transcriptomic signatures of prostate cancer progression: a comprehensive RNA-seq study.3 Biotech · 2025Article
- Role of Protein Phosphatases in Tumor Angiogenesis: Assessing PP1, PP2A, PP2B and PTPs Activity.International journal of molecular sciences · 2024Review
- DNA-methylation variability in normal mucosa: a field cancerization marker in patients with adenomatous polyps.Journal of the National Cancer Institute · 2024Article
- A novel peptide PDHK1-241aa encoded by circPDHK1 promotes ccRCC progression via interacting with PPP1CA to inhibit AKT dephosphorylation and activate the AKT-mTOR signaling pathway.Molecular cancer · 2024Article
- MicroRNA-22 Is a Key Regulator of Lipid and Metabolic Homeostasis.International journal of molecular sciences · 2023Article
- Nuclear PTEN Regulates Thymidylate Biosynthesis in Human Prostate Cancer Cell Lines.Metabolites · 2023Article
- Discovery of a Novel Bloom's Syndrome Protein (BLM) Inhibitor Suppressing Growth and Metastasis of Prostate Cancer.International journal of molecular sciences · 2022Article
- Association of mTORC1‑dependent circulating protein levels with cataract formation: a mendelian randomization study.BMC genomics · 2022Article
- Ubiquitin-specific proteases in inflammatory bowel disease-related signalling pathway regulation.Cell death & disease · 2022Review
- Ago-RIP Sequencing Identifies New MicroRNA-449a-5p Target Genes Increasing Sorafenib Efficacy in Hepatocellular Carcinoma.Journal of Cancer · 2022Article
- DNA methylation-based profiling reveals distinct clusters with survival heterogeneity in high-grade serous ovarian cancer.Clinical epigenetics · 2021Article
- Interception Targets ofCancer prevention research (Philadelphia, Pa.) · 2021Article
- Downregulation of lncRNA TSLNC8 promotes melanoma resistance to BRAF inhibitor PLX4720 through binding with PP1α to re-activate MAPK signaling.Journal of cancer research and clinical oncology · 2021Article
- Identification and validation of a five apoptosis-related genes signature for prediction of disease-free survival for testicular germ cell tumors.Translational andrology and urology · 2021Article
- Review
- PPP1R14B Is a Prognostic and Immunological Biomarker in Pan-Cancer.Frontiers in genetics · 2021Article
- ITCH as a potential therapeutic target in human cancers.Seminars in cancer biology · 2020Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
The mitogen-activated protein kinase (MAPK) pathway is frequently aberrantly activated in advanced cancers, including metastatic prostate cancer (CaP). However, activating mutations or gene rearrangements among MAPK signaling components, such as Ras and Raf, are not always observed in cancers with hyperactivated MAPK. The mechanisms underlying MAPK activation in these cancers remain largely elusive. Here we discover that genomic amplification of the PPP1CA gene is highly enriched in metastatic human CaP. We further identify an S6K/PP1α/B-Raf signaling pathway leading to activation of MAPK signaling that is antagonized by the PML tumor suppressor. Mechanistically, we find that PP1α acts as a B-Raf activating phosphatase and that PML suppresses MAPK activation by sequestering PP1α into PML nuclear bodies, hence repressing S6K-dependent PP1α phosphorylation, 14-3-3 binding and cytoplasmic accumulation. Our findings therefore reveal a PP1α/PML molecular network that is genetically altered in human cancer towards aberrant MAPK activation, with important therapeutic implications.
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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.