Hepatocyte growth factor/scatter factor (HGF/SF) and its receptor, the cMET tyrosine kinase participate in cancer invasion, angiogenesis and metastasis in a wide variety of neoplastic cells.
We provide evidence that (a) uncleavable SF inhibits both protease-mediated pro-SF conversion and active SF-induced Met activation; (b) local expression of uncleavable SF in tumors suppresses tumor growth, impairs tumor angiogenesis, and prevents metastatic dissemination; and (c) systemic expression of uncleavable SF dramatically inhibits the growth of transplanted tumors and abolishes the formation of spontaneous metastases without perturbing vital physiological functions.
These results suggest that E1AF activates the Rho/ROCK pathway in an HGF-enhanced manner and its activation is important in E1AF-induced motility and invasion as well as tumorigenesis and metastasis in NSCLC cells.
Inappropriate expression of the receptor tyrosine kinase Met and its ligand hepatocyte growth factor (HGF)/scatter factor (SF) is usually associated with an aggressive solid tumor phenotype (angiogenesis, invasiveness, and metastasis) and poor clinical prognosis.
HGF x CDK4(R24C) mice rapidly develop multiple invasive melanomas in the skin following neonatal carcinogen treatment, which spontaneously metastasize to lymph nodes and lungs.
These findings suggest that approximately half of all human glioblastomas respond to hypoxia with an induction of c-Met, which can enhance the stimulating effect of SF/HGF on tumor cell migration.
Based on the background that hepatocyte growth factor (HGF) and Met/HGF receptor tyrosine kinase play a definite role in tumor invasion and metastasis, NK4 was isolated as a competitive antagonist against functional association between HGF and Met.
Combination of AAV-HGFK1 and Ad-p53 significantly prolonged the survival of the mice and also significantly inhibited primary and secondary tumor growth.
The MET proto-oncogene, encoding the tyrosine kinase receptor for hepatocyte growth factor (HGF), senses unfavorable micro-environmental conditions and drives cell invasion and metastasis.
Angiogenesis plays an essential role in tumor growth and metastasis and is a promising target for cancer therapy. c-Met, a receptor tyrosine kinase, and its ligand, hepatocyte growth factor (HGF), are critical in cellular proliferation, motility, invasion, and angiogenesis.
MACC1 acts as a key regulator of the metastasis-inducing HGF/Met pathway, predicts the risk for metastasis in early cancer stages, and represents a novel target to attack metastasis.
In order to investigate roles of HGF signaling in tumor progression and metastasis, we measured effects of a specific MEK1 inhibitor (PD 098059) and a p38 kinase inhibitor (SB 203580) on HGF-mediated cell proliferation and MMP-9.
It has been reported that tetraspanin CD151 acts as a promoter of metastasis in several tumors and plays an important role in c-Met/hepatocyte growth factor signaling.