ArticleMolecular and cellular biology2000
Disassociation of met-mediated biological responses in vivo: the natural hepatocyte growth factor/scatter factor splice variant NK2 antagonizes growth but facilitates metastasis.
Article in Molecular and cellular biology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 57 citations in OpenAlex.
- H1/pHGFK1 nanoparticles exert anti-tumoural and radiosensitising effects by inhibition of MET in glioblastoma.British journal of cancer · 2018Article
- Hepatocyte growth factor and alternative splice variants - expression, regulation and implications in osteogenesis and bone health and repair.Expert opinion on therapeutic targets · 2016Review
- The hepatocyte growth factor isoform NK2 activates motogenesis and survival but not proliferation due to lack of Akt activation.Cellular signalling · 2016Article
- Expression array analysis of the hepatocyte growth factor invasive program.Clinical & experimental metastasis · 2015Article
- Physiological Signaling and Structure of the HGF Receptor MET.Biomedicines · 2014Review
- Hepatocyte Growth Factor Isoforms in Tissue Repair, Cancer, and Fibrotic Remodeling.Biomedicines · 2014Review
- HGF-MET cascade, a key target for inhibiting cancer metastasis: the impact of NK4 discovery on cancer biology and therapeutics.International journal of molecular sciences · 2013Article
- Targeting the HGF-cMET Axis in Hepatocellular Carcinoma.International journal of hepatology · 2013Article
- Targeting MET in cancer: rationale and progress.Nature reviews. Cancer · 2012Review
- Structural basis for agonism and antagonism of hepatocyte growth factor.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- Noncoding mutations of HGF are associated with nonsyndromic hearing loss, DFNB39.American journal of human genetics · 2009Article
- Overexpression of NK2 inhibits liver regeneration after partial hepatectomy in mice.World journal of gastroenterology · 2005Article
- Lifetime exposure to a soluble TGF-beta antagonist protects mice against metastasis without adverse side effects.The Journal of clinical investigation · 2002Article
- SF/HGF-c-Met autocrine and paracrine promote metastasis of hepatocellular carcinoma.World journal of gastroenterology · 2001Article
- Ligand discrimination by ErbB receptors: differential signaling through differential phosphorylation site usage.Oncogene · 2000Review
- MET molecular mechanisms and therapies in lung cancer.Cell adhesion & migrationReview
- Characterization of an Oncolytic Adenovirus Vector Constructed to Target the cMet Receptor.Oncolytic virotherapyArticle
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Hepatocyte growth factor/scatter factor (HGF/SF) stimulates numerous cellular activities capable of contributing to the metastatic phenotype, including growth, motility, invasiveness, and morphogenetic transformation. When inappropriately expressed in vivo, an HGF/SF transgene induces numerous hyperplastic and neoplastic lesions. NK1 and NK2 are natural splice variants of HGF/SF; all interact with a common receptor, Met. Although both agonistic and antagonistic properties have been ascribed to each isoform in vitro, NK1 retains the full spectrum of HGF/SF-like activities when expressed as a transgene in vivo. Here we report that transgenic mice broadly expressing NK2 exhibit none of the phenotypes characteristic of HGF/SF or NK1 transgenic mice. Instead, when coexpressed in NK2-HGF/SF bitransgenic mice, NK2 antagonizes the pathological consequences of HGF/SF and discourages the subcutaneous growth of transplanted Met-containing melanoma cells. Remarkably, the metastatic efficiency of these same melanoma cells is dramatically enhanced in NK2 transgenic host mice relative to wild-type recipients, rivaling levels achieved in HGF/SF and NK1 transgenic hosts. Considered in conjunction with reports that in vitro NK2 induces scatter, but not other activities, these data strongly suggest that cellular motility is a critical determinant of metastasis. Moreover, our results demonstrate how alternatively structured ligands can be exploited in vivo to functionally dissociate Met-mediated activities and their downstream pathways.
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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.