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Hepatocyte growth factor and Met in tumor biology and therapeutic approach with NK4
- Source :
- PROTEOMICS. 8:3360-3370
- Publication Year :
- 2008
- Publisher :
- Wiley, 2008.
-
Abstract
- 金沢大学がん研究所分子標的がん医療研究開発センター<br />Hepatocyte growth factor (HGF) and Met/HGF receptor tyrosine kinase play a role in the progression to invasive and metastatic cancers. A variety of cancer cells secrete molecules that enhance HGF expression in stromal fibroblasts, while fibroblast-derived HGF, in turn, is a potent stimulator of the invasion of cancer cells. In addition to the ligand-dependent activation, Met receptor activation is negatively regulated by cell-cell contact and Ser985 phosphorylation in the juxtamembrane of Met. The loss of intercellular junctions may facilitate an escape from the cell-cell contact-dependent suppression of Met-signaling. Significance of juxtamembrane mutations found in human cancers is assumed to be a loss-of-function in the negative regulation of Met. In attempts to block the malignant behavior of cancers, NK4 was isolated as a competitive antagonist against HGF-Met signaling. Independently on its HGF-antagonist action, NK4 inhibited angiogenesis induced by vascular endothelial cell growth factor and basic fibroblast growth factor, as well as HGF. In experimental models of distinct types of cancers, NK4 inhibited Met activation and this was associated with inhibition of tumor invasion and metastasis. NK4 inhibited tumor angiogenesis, thereby suppressing angiogenesis-dependent tumor growth. Cancer treatment with NK4 suppresses malignant tumors to be "static" in both tumor growth and spreading. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA.
- Subjects :
- medicine.medical_specialty
Angiogenesis
Basic fibroblast growth factor
NK4
Biology
Models, Biological
Biochemistry
Tumor angiogenesis
Metastasis
chemistry.chemical_compound
Neoplasms
Internal medicine
medicine
Humans
HGF
Neoplasm Metastasis
Molecular Biology
Hepatocyte Growth Factor
Cancer
Proto-Oncogene Proteins c-met
medicine.disease
Endocrinology
chemistry
Cancer cell
Met
Cancer research
Phosphorylation
Hepatocyte growth factor
Tyrosine kinase
medicine.drug
Subjects
Details
- ISSN :
- 16159861 and 16159853
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- PROTEOMICS
- Accession number :
- edsair.doi.dedup.....288e09a3e4b0d044861739dd991ea29e