Of the five target genes that were enriched in the glioblastoma pathway, in the WikiPathway database, both HRas proto-oncogene, GTPase and MET proto-oncogene, receptor tyrosine kinase target genes of hsa-miR-139-5p, were found to be significantly associated with patient survival.
Our studies reveal a novel mechanism to alter the recycling process of MET in glioblastoma cancer cells by promoting the receptor degradation through a proteasome-sensitive and lysosome-dependent pathway through the ligand-independent activation of MET using anti-MET antibodies.
Finally, combined treatment with BH3-mimetics and c-MET inhibitors results in significantly smaller tumors than each treatment alone in a PDX model system of glioblastoma.
H1/pHGFK1 exerts anti-tumoural and radiosensitive activities mainly through the inhibition and reversal of IR-induced MET and ATM-Chk2 axis activities in glioblastoma.
Previously, it was demonstrated that treatment with cabozantinib (MET/VEGFR2/RET inhibitor) prolonged survival of mice carrying orthotopic patient-derived xenografts (PDX) of the MET-addicted glioblastoma model E98, yet did not prevent development of recurrent and cabozantinib-resistant tumors.
In contrast to the classical subtype of primary glioblastoma, the cases studied here were characterized by the absence of EGFR amplification, PTEN loss, and 9p homozygous deletion and overexpression of p53, PDGFRα, and c-MET, suggesting that they can be classified as the proneural or mesenchymal subtype of glioblastoma and benefit from intensive therapy that includes temozolomide.
MET gain was detected in primary glioblastomas (47%) and secondary glioblastomas (44%), suggesting that this genetic alteration plays a role in the pathogenesis of both glioblastoma subtypes.
We investigated the molecular factors and pathway activation signatures that determine sensitivity to c-MET inhibitors in a panel of glioblastoma and medulloblastoma cells, glioblastoma stem cells, and established cell line-derived xenografts using functional assays, reverse protein microarrays, and in vivo tumor volume measurements, but validation with animal survival analyses remains to be done.
Here, we review findings that associate MET expression and activity with a specific, genetically defined glioblastoma stem cell subtype, and data showing how MET sustains the stem cell phenotype in glioblastoma and other tumors.
In this study, we found that expression of the MET oncogene was associated with neurospheres expressing the gene signature of mesenchymal and proneural subtypes of glioblastoma.
We investigated the effect of HGF/SF on matrix metalloproteinase-2 (MMP-2), membrane type 1 matrix metalloproteinase (MT1-MMP) and tissue inhibitors of metalloproteinases (TIMPs), expressions of c-Met/HGF receptor-positive human glioblastoma cells.