ArticleMolecular and cellular biology2000
Enhanced transformation by a plasma membrane-associated met oncoprotein: activation of a phosphoinositide 3'-kinase-dependent autocrine loop involving hyaluronic acid and CD44.
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 20 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
20 citing papers in PubMed, 53 citations in OpenAlex.
- Androgen Receptor Regulates CD44 Expression in Bladder Cancer.Cancer research · 2021Article
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- Endothelial Grb2-associated binder 1 is crucial for postnatal angiogenesis.Arteriosclerosis, thrombosis, and vascular biology · 2011Article
- RasGRP3 contributes to formation and maintenance of the prostate cancer phenotype.Cancer research · 2010Article
- Clinical significance of pAKT and CD44v6 overexpression with breast cancer.Journal of cancer research and clinical oncology · 2010Article
- Phosphotyrosine signaling analysis of site-specific mutations on EGFRvIII identifies determinants governing glioblastoma cell growth.Molecular bioSystems · 2010Article
- Deletion of the ectodomain unleashes the transforming, invasive, and tumorigenic potential of the MET oncogene.Cancer science · 2009Article
- Membrane localization is critical for activation of the PICK1 BAR domain.Traffic (Copenhagen, Denmark) · 2008Article
- The phosphoinositide 3-kinase pathway in human cancer: genetic alterations and therapeutic implications.Current genomics · 2007Article
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- Membrane targeting of Grb2-associated binder-1 (Gab1) scaffolding protein through Src myristoylation sequence substitutes for Gab1 pleckstrin homology domain and switches an epidermal growth factor response to an invasive morphogenic program.Molecular biology of the cell · 2003Article
- Oncogenic targeting of an activated tyrosine kinase to the Golgi apparatus in a glioblastoma.Proceedings of the National Academy of Sciences of the United States of America · 2003Article
- Hepatocyte growth factor switches orientation of polarity and mode of movement during morphogenesis of multicellular epithelial structures.Molecular biology of the cell · 2003Article
- Hyaluronan and tumor growth.The American journal of pathology · 2002Article
- Dysregulation of Met receptor tyrosine kinase activity in invasive tumors.The Journal of clinical investigation · 2002Review
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- Hyaluronan is not just a goo!The Journal of clinical investigation · 2000Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A Met-hepatocyte growth factor receptor oncoprotein, Tpr-Met, generated by chromosomal rearrangement, fuses a protein dimerization motif with the cytoplasmic domain of the Met receptor, producing a cytosolic, constitutively activated tyrosine kinase. Although both the Met receptor and the Tpr-Met oncoprotein associate with the same substrates, activating mutations of the Met receptor in hereditary papillary renal carcinomas have different signaling requirements for transformation than Tpr-Met. This suggests differential activation of membrane-localized pathways by oncogenic forms of the membrane-bound Met receptor but not by the cytoplasmic Tpr-Met oncoprotein. To establish which pathways might be differentially regulated, we have localized the constitutively activated Tpr-Met oncoprotein to the membrane using the c-src myristoylation signal. Membrane localization enhances cellular transformation, focus formation, and anchorage-independent growth and induces tumors with a distinct myxoid phenotype. This correlates with the induction of hyaluronic acid (HA) and the presence of a distinct form of its receptor, CD44. A pharmacological inhibitor of phosphoinositide 3' kinase (PI3'K), inhibits the production of HA, and conversely, an activated, plasma membrane-targeted form of PI3'K is sufficient to enhance HA production. Furthermore, the multisubstrate adapter protein Gab-1, which couples the Met receptor with PI3'K, enhances Met receptor-dependent HA synthesis in a PI3'K-dependent manner. These results provide a positive link to a role for HA and CD44 in Met receptor-mediated oncogenesis and implicate PI3'K in these events.
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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.