ArticleInternational journal of cancer2011
Metastasis suppressor function of NM23-H1 requires its 3'-5' exonuclease activity.
Article in International journal of cancer, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 69 citations in OpenAlex.
- Evaluation of serum nucleoside diphosphate kinase A for the detection of colorectal cancer.Scientific reports · 2016Trial
- Nonmetastatic cell 1 gene polymorphisms are associated with the clinical progression and prognoses of patients with colorectal cancer.Frontiers in genetics · 2025Article
- Mechanisms of action of NME metastasis suppressors - a family affair.Cancer metastasis reviews · 2023Review
- Metastasis suppressor genes in clinical practice: are they druggable?Cancer metastasis reviews · 2023Review
- Patient-derived xenograft culture-transplant system for investigation of human breast cancer metastasis.Communications biology · 2021Article
- Article
- Comprehensive analysis of theTranslational cancer research · 2020Article
- Structure, Folding and Stability of Nucleoside Diphosphate Kinases.International journal of molecular sciences · 2020Review
- Metastasis Suppressor NME1 Modulates Choice of Double-Strand Break Repair Pathways in Melanoma Cells by Enhancing Alternative NHEJ while Inhibiting NHEJ and HR.International journal of molecular sciences · 2020Article
- The Subcellular Localization and Oligomerization Preferences of NME1/NME2 upon Radiation-Induced DNA Damage.International journal of molecular sciences · 2020Article
- The Function of NM23-H1/NME1 and Its Homologs in Major Processes Linked to Metastasis.Pathology oncology research : POR · 2020Review
- NME1 Drives Expansion of Melanoma Cells with Enhanced Tumor Growth and Metastatic Properties.Molecular cancer research : MCR · 2019Article
- Metastasis Suppressor NME1 Directly Activates Transcription of theAnticancer research · 2018Article
- Small molecule activator of Nm23/NDPK as an inhibitor of metastasis.Scientific reports · 2018Article
- A competitive cell-permeable peptide impairs Nme-1 (NDPK-A) and Prune-1 interaction: therapeutic applications in cancer.Laboratory investigation; a journal of technical methods and pathology · 2018Review
- Identification of a gene expression signature associated with the metastasis suppressor function of NME1: prognostic value in human melanoma.Laboratory investigation; a journal of technical methods and pathology · 2018Article
- Metastasis suppressors: functional pathways.Laboratory investigation; a journal of technical methods and pathology · 2018Review
- The dosage-dependent effect exerted by the NM23-H1/H2 homolog NDK-1 on distal tip cell migration in C. elegans.Laboratory investigation; a journal of technical methods and pathology · 2018Review
- Nuclear functions of NME proteins.Laboratory investigation; a journal of technical methods and pathology · 2018Review
- Plant nucleoside diphosphate kinase 1: A housekeeping enzyme with moonlighting activity.Plant signaling & behavior · 2018Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The metastasis suppressor NM23-H1 possesses 3 enzymatic activities in vitro, a nucleoside diphosphate kinase (NDPK), a protein histidine kinase and a more recently characterized 3'-5' exonuclease. Although the histidine kinase has been implicated in suppression of motility in breast carcinoma cell lines, potential relevance of the NDPK and 3'-5' exonuclease to metastasis suppressor function has not been addressed in detail. To this end, site-directed mutagenesis and biochemical analyses of bacterially expressed mutant NM23-H1 proteins have identified mutations that disrupt the 3'-5' exonuclease alone (Glu(5) to Ala, or E(5) A), the NDPK and histidine kinase activities tandemly (Y(52) A, H(118) F) or all 3 activities simultaneously (K(12) Q). Although forced expression of NM23-H1 potently suppressed spontaneous lung metastasis of subcutaneous tumor explants derived from the human melanoma cell line 1205LU, no significant metastasis suppressor activity was obtained with the exonuclease-deficient variants E(5) A and K(12) Q. The H(118) F mutant, which lacked both the NDPK and histidine kinase while retaining the 3'-5' exonuclease, also exhibited compromised suppressor activity. In contrast, each mutant retained the ability to suppress motility and invasive characteristics of 1205LU cells in culture, indicating that the NM23-H1 molecule possesses an additional activity(s) mediating these suppressor functions. These studies provide the first demonstration that the 3'-5' exonuclease activity of NM23-H1 is necessary for metastasis suppressor function and further indicate cooperativity of the 3 enzymatic activities of the molecule on suppression of the metastatic process.
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