ArticleThe Journal of clinical investigation2014
Membrane protein CNNM4-dependent Mg2+ efflux suppresses tumor progression.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 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
70 citing papers in PubMed, 114 citations in OpenAlex.
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
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- Phosphatases of regenerating liver downregulate PTEN to promote tumorigenesis.Biochemical Society transactions · 2026Review
- Altered Magnesium Environments Restrict Colorectal HT-29 Spheroid Growth by Disturbing Cellular MgInternational journal of molecular sciences · 2026Article
- Transient receptor potential melastatin 6 and transient receptor potential melastatin 6/7 antagonists suppress colon adenocarcinoma HT-29 cells.World journal of gastrointestinal oncology · 2025Article
- microRNAs Regulate Cellular Magnesium by Tuning Expression of the Plasma Membrane Protein CNNM4.ACS chemical biology · 2025Article
- The PACT Network: PRL, ARL, CNNM, and TRPM Proteins in Magnesium Transport and Disease.International journal of molecular sciences · 2025Review
- Unlocking TRPM7 interactions: A database-driven quest.Computational and structural biotechnology journal · 2025Review
- Differential regulation of magnesium transporters Slc41, Cnnm and Trpm6-7 in the kidney of salmonids may represent evolutionary adaptations to high salinity environments.BMC genomics · 2024Article
- Development of a high-throughput screening system targeting the protein-protein interactions between PRL and CNNM.Scientific reports · 2024Article
- Magnesium Ion: A New Switch in Tumor Treatment.Biomedicines · 2024Review
- PTP4A2 Promotes Glioblastoma Progression and Macrophage Polarization under Microenvironmental Pressure.Cancer research communications · 2024Article
- Targeting PRL phosphatases in hematological malignancies.Expert opinion on therapeutic targets · 2024Review
- Targeting Moonlighting Enzymes in Cancer.Molecules (Basel, Switzerland) · 2024Review
- Dimerization of the CNNM extracellular domain.Protein science : a publication of the Protein Society · 2024Article
- Prognostic significance of CNNM4 in ovarian cancer: a comprehensive bioinformatics analysis.Frontiers in oncology · 2024Article
- Phosphatase and Pseudo-Phosphatase Functions of Phosphatase of Regenerating Liver 3 (PRL-3) Are Insensitive to Divalent Metals In Vitro.ACS omega · 2023Article
- Structural insights into regulation of CNNM-TRPM7 divalent cation uptake by the small GTPase ARL15.eLife · 2023Article
- PRL-1/2 phosphatases control TRPM7 magnesium-dependent function to regulate cellular bioenergetics.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
10 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intracellular Mg(2+) levels are strictly regulated; however, the biological importance of intracellular Mg(2+) levels and the pathways that regulate them remain poorly understood. Here, we determined that intracellular Mg(2+) is important in regulating both energy metabolism and tumor progression. We determined that CNNM4, a membrane protein that stimulates Mg(2+) efflux, binds phosphatase of regenerating liver (PRL), which is frequently overexpressed in malignant human cancers. Biochemical analyses of cultured cells revealed that PRL prevents CNNM4-dependent Mg(2+) efflux and that regulation of intracellular Mg(2+) levels by PRL and CNNM4 is linked to energy metabolism and AMPK/mTOR signaling. Indeed, treatment with the clinically available mTOR inhibitor rapamycin suppressed the growth of cancer cells in which PRL was overexpressed. In ApcΔ(14/+) mice, which spontaneously form benign polyps in the intestine, deletion of Cnnm4 promoted malignant progression of intestinal polyps to adenocarcinomas. IHC analyses of tissues from patients with colon cancer demonstrated an inverse relationship between CNNM4 expression and colon cancer malignancy. Together, these results indicate that CNNM4-dependent Mg(2+) efflux suppresses tumor progression by regulating energy metabolism.
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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.