ArticleOncogene2015
The protein tyrosine phosphatase PRL-2 interacts with the magnesium transporter CNNM3 to promote oncogenesis.
Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 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
72 citing papers in PubMed, 121 citations in OpenAlex.
- Article
- Article
- Phosphatases of regenerating liver downregulate PTEN to promote tumorigenesis.Biochemical Society transactions · 2026Review
- Molecular bases of circadian magnesium rhythms across eukaryotes.FEBS letters · 2026Article
- Leishmania donovani's protein tyrosine phosphatases interact with DUF21 and respond to environmental magnesium.The FEBS journal · 2026Article
- Article
- Clinicopathological implications of miR-3127 in melanoma.Journal of pathology and translational medicine · 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
- Development of a high-throughput screening system targeting the protein-protein interactions between PRL and CNNM.Scientific reports · 2024Article
- PTP4A2 Promotes Glioblastoma Progression and Macrophage Polarization under Microenvironmental Pressure.Cancer research communications · 2024Article
- Micronutrient Status and Breast Cancer: A Narrative Review.International journal of molecular sciences · 2024Review
- Targeting PRL phosphatases in hematological malignancies.Expert opinion on therapeutic targets · 2024Review
- Dimerization of the CNNM extracellular domain.Protein science : a publication of the Protein Society · 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
- Homologs of Ancestral CNNM Proteins Affect Magnesium Homeostasis and Circadian Rhythmicity in a Model Eukaryotic Cell.International journal of molecular sciences · 2023Article
- Structural insights into regulation of TRPM7 divalent cation uptake by the small GTPase ARL15.bioRxiv : the preprint server for biology · 2023Article
12 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
9 authors at 5 institutions in 2 countries.
Funding
Abstract
The three PRL (phosphatases of regenerating liver) protein tyrosine phosphatases (PRL-1, -2 and -3) have been identified as key contributors to metastasis in several human cancers, yet the molecular basis of their pro-oncogenic property is unclear. Among the subfamily of PRL phosphatases, overexpression of PRL-2 in breast cancer cells has been shown to promote tumor growth by a mechanism that remains to be uncovered. Here we show that PRL-2 regulates intracellular magnesium levels by forming a functional heterodimer with the magnesium transporter CNNM3. We further reveal that CNNM3 is not a phosphorylated substrate of PRL-2, and that the interaction occurs through a loop unique to the CBS pair domains of CNNM3 that exists only in organisms having PRL orthologs. Supporting the role of PRL-2 in cellular magnesium transport is the observation that PRL-2 knockdown results in a substantial decrease of cellular magnesium influx. Furthermore, in PRL-2 knockout mice, serum magnesium levels were significantly elevated as compared with control animals, indicating a pivotal role for PRL-2 in regulating cellular magnesium homeostasis. Although the expression levels of CNNM3 remained unchanged after magnesium depletion of various cancer cell lines, the interaction between endogenous PRL-2 and CNNM3 was markedly increased. Importantly, xenograft tumor assays with CNNM3 and a mutant form that does not associate with PRL-2 confirm that CNNM3 is itself pro-oncogenic, and that the PRL-2/CNNM3 association is important for conferring transforming activities. This finding is further confirmed from data in human breast cancer tissues showing that CNNM3 levels correlate positively with both PRL-2 expression and the tumor proliferative index. In summary, we demonstrate that oncogenic PRL-2 controls tumor growth by modulating intracellular magnesium levels through binding with the CNNM3 magnesium transporter.
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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.