Cells stably transduced with anti-MET short hairpin RNA (shRNA) constructs were tested for growth and metastasis in severe combined immunodeficient (SCID) mice.
Chemoreagent or TKI treatment can lead to increased expression of hepatocyte growth factor (HGF) and/or MET, and this effect correlates with increased metastasis and poor prognosis.
Considering the role of proto-oncogene c-Met (c-Met) in oncogenesis, we examined the effects of the metastasis suppressor, N-myc downstream regulated gene-1 (NDRG1), and two NDRG1-inducing thiosemicarbazone-based agents, Dp44mT and DpC, on c-Met expression in DU145 and Huh7 cells.
EGFR and c-Met share the same downstream pathways and cooperate not only in promoting metastasis but also in conferring resistance to tyrosine kinase inhibitor (TKI) therapies in NSCLC.
Elevated activation of the receptor tyrosine kinase (RTK) MET is frequent in RMS and is thought to cause increased tumor metastasis and lack of differentiation.
Elevated protein levels in absence of gene amplification were not attributed to mutations, based on results of targeted next-generation sequencing.Our data reveal that clear-cell RCC with MET upregulation show an aggressive behavior and MET copy number increase is evident in a substantial percentage of patients with high-grade carcinomas and metastatic disease.
Emerging evidence indicates that hepatocyte growth factor receptor (or Met) pathway plays a pivotal role in HNSCC metastasis and resistance to chemotherapy.
Expression and activation of the canine Met receptor were studied utilizing immunohistochemical techniques in 39 samples of canine osteosarcoma, including 35 primary tumours and four metastases.
Expression of MET was analyzed in hormone-naive primary prostate cancers (N=481), lymph node (N=40) and bone (N=8) metastases, as well as HRPC (N=54) and bone metastases (N=15).
Expression of AIF inversely correlated with that of positive NSCLC markers, e.g., dihydrodiol dehydrogenase (DDH), c-MET, short oncostatin M receptor (OSMRs), matrix metalloproteinase (MMP)-1, and HER2/neu, which were closely associated with drug resistance, tumor recurrence, metastasis and poor prognosis.
For this purpose, tumor samples were analyzed for c-MET expression by immunohistochemistry (IHC), for c-MET copy number alterations by fluorescence in situ hybridization (FISH), and for c-MET mutations by next generation sequencing (NGS) in a retrospective cohort of 90 primary ccRCC of patients with metastases treated by first-line sunitinib.
Further studies indicated that the HGF/MET signaling pathway was involved in in vitro motility and invasion activities of the G3H cells and treatments with MET inhibitors decreased formation of distant metastases in our orthotopic model using G3H cells.
Furthermore, a significant increase in c-Met was seen in liver metastases compared with primary CRC (P<0.0001). c-Met gene amplification was observed in 2% (3/177) of localized cancers, 9% (6/70) of cancers with distant metastases (P<0.02), and 18% (25/147) of liver metastases (P<0.01).
Furthermore, reduced methylation of specific LINE-1 elements within the MET gene inversely correlated with induction of MET expression in CRC metastases (R=-0.44; p<0.0001).
Hepatocyte growth factor (HGF) is a stromal-derived cytokine that plays a crucial role in invasion and metastasis of tumor cells through the interaction with HGF receptor, c-Met, which is frequently overexpressed in pancreatic cancer.
Here, we demonstrate that vascular endothelial growth factor (VEGF) directly and negatively regulates tumor cell invasion through enhanced recruitment of the protein tyrosine phosphatase 1B (PTP1B) to a MET/VEGFR2 heterocomplex, thereby suppressing HGF-dependent MET phosphorylation and tumor cell migration.
HGF/SF is a multifunctional cytokine that enhances the metastatic behaviour of tumour cells in vitro by stimulation of the c-met receptor tyrosine kinase and has been implicated in the development of tumour metastasis in vivo.
HGF/SF-MET signaling is equally crucial for growth and metastasis of a variety of human tumors, but resistance to small-molecule inhibitors of MET kinase develops rapidly and therapeutic antibody targeting remains challenging.
High MET mRNA expression (score ≥3) was associated with lymph node metastasis (P = .014), distant metastasis (P = .001), and higher TNM stage (P<.001).