ArticleJournal of experimental & clinical cancer research : CR2010
Nm23-H1 suppresses hepatocarcinoma cell adhesion and migration on fibronectin by modulating glycosylation of integrin beta1.
Article in Journal of experimental & clinical cancer research : CR, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 34 citations in OpenAlex.
- Histidine Phosphorylation: Protein Kinases and Phosphatases.International journal of molecular sciences · 2024Review
- Mechanisms of action of NME metastasis suppressors - a family affair.Cancer metastasis reviews · 2023Review
- The Integrin Pathway Partially Mediates Stretch-Induced Deficits in Primary Rat Microglia.Molecular neurobiology · 2023Article
- Mechanical Confinement and DDR1 Signaling Synergize to Regulate Collagen-Induced Apoptosis in Rhabdomyosarcoma Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Tenascin-C fibronectin D domain is involved in the fine-tuning of glial response to CNS injuryFrontiers in cell and developmental biology · 2022Article
- Review
- Vascular smooth muscle cells direct extracellular dysregulation in aortic stiffening of hypertensive rats.Aging cell · 2018Article
- Characterization of a group I Nme protein of Capsaspora owczarzaki-a close unicellular relative of animals.Laboratory investigation; a journal of technical methods and pathology · 2018Article
- Clinical Implication and the Hereditary Factors of NM23 in Hepatocellular Carcinoma Based on Bioinformatics Analysis and Genome-Wide Association Study.Journal of oncology · 2018Article
- Imatinib induces up-regulation ofGastroenterology and hepatology from bed to bench · 2017Article
- Extract of Monascus purpureus CWT715 Fermented from Sorghum Liquor Biowaste Inhibits Migration and Invasion of SK-Hep-1 Human Hepatocarcinoma Cells.Molecules (Basel, Switzerland) · 2016Article
- Non-small-cell lung cancer cells combat epidermal growth factor receptor tyrosine kinase inhibition through immediate adhesion-related responses.OncoTargets and therapy · 2016Article
- Metastasis suppressor NME1 regulates melanoma cell morphology, self-adhesion and motility via induction of fibronectin expression.Experimental dermatology · 2015Article
- Regulation of the metastasis suppressor Nm23-H1 by tumor viruses.Naunyn-Schmiedeberg's archives of pharmacology · 2015Review
- NDK-1, the homolog of NM23-H1/H2 regulates cell migration and apoptotic engulfment in C. elegans.PloS one · 2014Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNm23 gene was isolated as a metastatic suppressor gene. The antimetastatic effect of Nm23 has been an enigma for more than 10 years. Little is known about its molecular mechanisms. In this study we overexpressed Nm23-H1 in H7721 cells and observed reduction of cell adhesion, migration and extension of actin stress fibers in cells stimulated by fibronectin (Fn).
methodspcDNA3/Nm23-H1 was introduced into H7721 cells, and expression of Nm23-H1 was monitored by RT-PCR and western blot. Cell adhesion, actin extension and wound-induced migration assays were done on dishes coated with fibronectin. Phosphorylation of focal adhesion kinase (FAK) and total amount of integrin alpha 5 and beta1 in Nm23-H1 transfected cells and control cells were measured by western blot. Flow cytometry was used to detect expression of surface alpha 5 and beta1 integrin. N-glycosylation inhibitor tunicamycin was used to deglycosylate the integrin beta1 subunit.
resultsOverexpression of nm23-H1 in H7721 cells reduced cell adhesion, migration and extension of actin stress fibers on dishes coated with Fn. Phosphorylation of FAK in Nm23-H1 transfected cells was also attenuated. Integrin alpha 5 and beta1 gene messages were unaltered in nm23-H1 overexpressed cells as detected by RT-PCR. However, while cell surface integrin alpha 5 was unchanged, surface expression of beta1 integrin was downregulated. Western blot also showed that the total amounts of integrin alpha 5 and beta1 were unaltered, but the level of mature integrin beta1 isoform was decreased significantly. Furthermore, partially glycosylated precursor beta1 was increased, which indicated that the impaired glycosylation of integrin beta1 precursor might contribute to the loss of cell surface integrin beta1 in nm23-H1 overexpressed cells.
conclusionThese results suggest that by modulating glycosylation of integrin beta1, nm23-H1 down-regulates integrin beta1 subunit on cell surface and mediates intracellular signaling and subsequent suppression of the invasive process, including cell adhesion and migration.
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