These observations suggest HGF-Met system is involved in the repair process of the inflamed mucosa of UC and provide further support for the view that the inappropriate expressions of both HGF and c-met genes predispose to the development of colorectal cancer in patients with UC.
Overexpression of c-met protein in colorectal cancers is combined with an expression of HGF in the majority of cases suggesting a paracrine manner of growth enhancement, while only a weak expression of c-met or HGF was detected in metastatic tissues.
The absence of detectable Met protein expression in adenomas of Apc+/min mice contrasts sharply with the vast overexpression of the protein in adenomas of humans with familial adenomatous polyposis or sporadic colorectal carcinomas.
Overexpressed or activated hepatocyte growth factor receptor, encoded by the MET proto-oncogene, was found in the majority of colorectal carcinomas (CRCs), whose stepwise progression to malignancy requires transcriptional activation of beta-catenin.
However, investigation of this dynamic reversible EMT and MET that underpins CRC morphogenesis has been hindered by a lack of suitable in vitro models.
Slight increases in c-Met copy number can be detected in localized CRCs, but gene amplification is largely restricted to Stage IV primary cancers and liver metastases. c-Met gene amplification is linked to metastatic progression, and is a viable target for a significant subset of advanced CRC.
High resolution mass spectrometry was used to characterize immunoaffinity-purified, phosphotyrosine (pY)-containing tryptic peptides of the MET-expressing CRC cell model, DLD1.
Amplified genes were noted in 37% of gastric/esophageal tumors, including in therapeutically targetable kinases such as ERBB2, FGFR1, FGFR2, EGFR, and MET, suggesting the potential use of genomic amplifications as biomarkers to guide therapy of gastric and esophageal cancers where targeted therapeutics have been less developed compared with colorectal cancers.
We show that miR-1 can have a tumor suppressor function in colorectal cancer by directly downregulating MET oncogene both at RNA and protein level and that reexpression of miR-1 leads to MET-driven reduction of cell proliferation and motility, identifying the miR-1 downmodulation as one of the events that could enhance colorectal cancer progression.
Starting January 1, 2012, preemptive biomarker profiling was offered at the West German Cancer Center to all patients with advanced non-small-cell lung (NSCLC) or colorectal cancer (CRC), who met generic study inclusion criteria.
The combined inhibition of EGFR and MET receptor could represent a strategy for preventing and/or overcoming cetuximab resistance in patients with colorectal cancer.
These results highlight the role of MET in mediating primary and secondary resistance to anti-EGFR therapies in colorectal cancer and encourage the use of MET inhibitors in patients displaying resistance as a result of MET amplification.
Moreover, the data suggested that the combination of c-Met-targeted therapy with chemotherapy or irradiation might be an effective strategy against colorectal cancer harboring a KRAS mutation.
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).
Further analyses identified acute increases in c-MET activity following treatment with MEK inhibitors in KRASMT CRC models, which was demonstrated to promote JAK1/2-STAT3-mediated resistance.
KRAS coding exons in 61 treatment-naive colorectal cancer (CRC) tumors and KRAS, EGFR, ALK, and MET in lung tumors from three Chinese non-small cell lung cancer (NSCLC) patients were sequenced using ultradeep sequencing methods.
The presented data subclassified CRCs based on their activated signaling pathways and identify a role for c-MET and IGF1R-driven PI3K signaling in CRCs, which is superior to KRAS mutational tests alone.