ArticlePloS one2014
Activated cMET and IGF1R-driven PI3K signaling predicts poor survival in colorectal cancers independent of KRAS mutational status.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Pooled it
- Article
- First-in-human phase I trial of anti-hepatocyte growth factor antibody (YYB101) in refractory solid tumor patients.Therapeutic advances in medical oncology · 2020Article
- Role of anabolic agents in colorectal carcinogenesis: Myths and realities (Review).Oncology reports · 2019Review
- Combination of Docetaxel Plus Savolitinib in Refractory Cancer Patients: A Report on Phase I Trial.Translational oncology · 2019Article
- The prognostic and therapeutic role of hormones in colorectal cancer: a review.Molecular biology reports · 2019Review
- Protein Tyrosine Signaling and its Potential Therapeutic Implications in Carcinogenesis.Current pharmaceutical design · 2017Review
- Stromal-derived IGF2 promotes colon cancer progression via paracrine and autocrine mechanisms.Oncogene · 2017Article
- Dual inhibition of MET and SRC kinase activity as a combined targeting strategy for colon cancer.Experimental and therapeutic medicine · 2017Article
- Comparative proteomics of a model MCF10A-KRasG12V cell line reveals a distinct molecular signature of the KRasG12V cell surface.Oncotarget · 2016Article
- Identifying the Appropriate FISH Criteria for Defining MET Copy Number-Driven Lung Adenocarcinoma through Oncogene Overlap Analysis.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2016Article
- Targeting colorectal cancer via its microenvironment by inhibiting IGF-1 receptor-insulin receptor substrate and STAT3 signaling.Oncogene · 2016Article
- Molecular characterization of colorectal cancer patients and concomitant patient-derived tumor cell establishment.Oncotarget · 2016Article
- Atypical Diabetic Foot Ulcer Keratinocyte Protein Signaling Correlates with Impaired Wound Healing.Journal of diabetes research · 2016Article
- MiR-144 Inhibits Uveal Melanoma Cell Proliferation and Invasion by Regulating c-Met Expression.PloS one · 2015Article
- Retrospective Review of MET Gene Mutations.Oncoscience · 2015Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundOncogenic mutational analysis provides predictive guidance for therapeutics such as anti-EGFR antibodies, but it is successful only for a subset of colorectal cancer (CRC) patients.
methodA comprehensive molecular profiling of 120 CRC patients, including 116 primary, 15 liver metastasis, and 1 peritoneal seeding tissue samples was performed to identify the relationship between v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) WT and mutant CRC tumors and clinical outcomes. This included determination of the protein activation patterns of human epidermal receptor 1 (HER1), HER2, HER3, c-MET, insulin-like growth factor 1 receptor (IGF1R), phosphatidylinositide 3-kinase (PI3K), Src homology 2 domain containing (Shc), protein kinase B (AKT), and extracellular signal-regulated kinase (ERK) kinases using multiplexed collaborative enzyme enhanced reactive (CEER) immunoassay.
resultsKRAS WT and mutated CRCs were not different with respect to the expression of the various signaling molecules. Poor prognosis in terms of early relapse (<2 years) and shorter disease-free survival (DFS) correlated with enhanced activation of PI3K signaling relative to the HER kinase pathway signaling, but not with the KRAS mutational status. KRAS WT CRCs were identified as a mixed prognosis population depending on their level of PI3K signaling. KRAS WT CRCs with high HER1/c-MET index ratio demonstrated a better DFS post-surgery. c-MET and IGF1R activities relative to HER axis activity were considerably higher in early relapse CRCs, suggesting a role for these alternative receptor tyrosine kinases (RTKs) in driving high PI3K signaling.
conclusionsThe 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. The results from this study can be utilized to identify aggressive CRCs, explain failure of currently approved therapeutics in specific CRC subsets, and, most importantly, generate hypotheses for pathway-guided therapeutic strategies that can be tested clinically.
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