Using <i>in vitro</i> 3D type I collagen cultures of human colorectal cancer (CRC) cell line HCA-7 derivatives CC, SC, and CC-CR, we previously identified that activation of receptor tyrosine kinases (RTKs) MET and RON contributed to resistance to the EGF receptor (EGFR)-directed therapeutic antibody cetuximab.
In vitro results demonstrated that KPNB1 decreasing markedly reduced CRC cell proliferation, migration and invasion, which was positively associated with the expression of MET proto-oncogene (MET).
Cell spiking assay and RT-PCR were performed with blood samples from healthy volunteers spiked with six CRC cell lines to generate an algorithm, herein called the Six-gene Assay, based on six genes (CEA, EpCAM, CK19, MUC1, EGFR and C-Met) for CTC detection.
Compelling clinical and experimental evidence suggest that aberrant engagement of cell surface growth factor receptor tyrosine kinase (RTK) signaling, like that of the hepatocyte growth factor (HGF)/MET receptor, underlies CRC metastatic progression by promoting these cancer hallmarks.
Long intergenic non-protein coding RNA 1510, an enhancer lncRNA (LINC01510), a lncRNA enhancer is upregulated in colorectal cancer (CRC), and its expression might relate to MET as revealed by lncRNA microarray data.
Comparative analysis of the EGFR, HER2, c-MYC, and MET variations in colorectal cancer determined by three different measures: gene copy number gain, amplification status and the 2013 ASCO/CAP guideline criterion for HER2 testing of breast cancer.
Amplification-dependent overexpression of 64 known driver oncogenes were found in 587 tumors (40%); genes frequently observed were MYC (25%) and MET (18%) in colorectal cancer; SKP2 (21%) in lung squamous cell carcinoma; HIST1H3B (19%) and MYCN (13%) in liver cancer; KIT (57%) in gastrointestinal stromal tumors; and FOXL2 (12%) in squamous cell carcinoma across tissues.
This review will describe the mechanisms of aberrant c-Met signaling in colorectal cancer and discuss on additional roles for c-Met receptor through crosstalk with other tyrosine kinase receptors and cell surface proteins in colorectal cancer.
Latest but not lifetime leisure time physical activity [in metabolic task hours per week (MET-h/wk)] was associated with decreased overall and CRC-specific mortality (>56.2 vs. ≤13.2 MET-h/wk: adjusted hazard ratio (aHR)<sub>Overall/latest</sub> = 0.75; 95% confidence interval (CI) = 0.61-0.91; aHR<sub>CRC-specific/latest</sub> = 0.81; 95% CI = 0.64-1.02).
Therapeutic efficacy of SYM004, a mixture of two anti-EGFR antibodies in human colorectal cancer with acquired resistance to cetuximab and MET activation.
MET amplification is here identified-clinically and preclinically-as a new mechanism of resistance to EGFR and BRAF dual/triple block combinations in BRAF-mutated colorectal cancer.
Tissue samples of 51 PM and 33 paired primary CRCs were stained immunohistochemically for c-MET and phosphorylated signal transducer and activator of transcription 3 (pSTAT3).
This data also indicates that RNA ISH, but not immunohistochemistry, provides a robust methodology to assess MET levels as a potential driving force of CRC tumor invasion and metastasis.