ArticleNeoplasia (New York, N.Y.)2010
Oncogenic KRAS desensitizes colorectal tumor cells to epidermal growth factor receptor inhibition and activation.
Article in Neoplasia (New York, N.Y.), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 50 citations in OpenAlex.
- Extracellular Vesicle-Derived microRNAs: Novel Non-Invasive Biomarkers for Gastrointestinal Malignancies.International journal of molecular sciences · 2025Review
- Review
- Metastasis of colon cancer requires Dickkopf-2 to generate cancer cells with Paneth cell properties.eLife · 2024Article
- Metastasis of colon cancer requires Dickkopf-2 to generate cancer cells with Paneth cell properties.bioRxiv : the preprint server for biology · 2024Article
- Simultaneous Imaging and Therapy Using Epitope-Specific Anti-Epidermal Growth Factor Receptor (EGFR) Antibody Conjugates.Pharmaceutics · 2022Article
- Efficacy of Combined Use of Everolimus and Second-Generation Pan-EGRF Inhibitors inInternational journal of molecular sciences · 2022Article
- Argonaute 2 modulates EGFR-RAS signaling to promote mutantPNAS nexus · 2022Article
- Pathway profiling of a novel SRC inhibitor, AZD0424, in combination with MEK inhibitors for cancer treatment.Molecular oncology · 2022Article
- Modeling Adaptive Resistance of KRAS Mutant Colorectal Cancer to MAPK Pathway Inhibitors with a Three-Dimensional Tumor Model.ACS pharmacology & translational science · 2020Article
- Repurposing of Cetuximab in antibody-directed chemotherapy-loaded nanoparticles in EGFR therapy-resistant pancreatic tumours.Nanoscale · 2019Article
- Single-cell RNA-seq variant analysis for exploration of genetic heterogeneity in cancer.Scientific reports · 2019Article
- Therapeutic potential of nimotuzumab PEGylated-maytansine antibody drug conjugates against EGFR positive xenograft.Oncotarget · 2019Article
- Synthesis, Molecular Docking and Anticancer Activity of Diflunisal Derivatives as Cyclooxygenase Enzyme Inhibitors.Molecules (Basel, Switzerland) · 2018Article
- LGR5 expression is regulated by EGF in early colorectal adenomas and governs EGFR inhibitor sensitivity.British journal of cancer · 2018Article
- The K-Ras effector p38γ MAPK confers intrinsic resistance to tyrosine kinase inhibitors by stimulatingThe Journal of biological chemistry · 2017Article
- Article
- Evaluation of antibody-dependent cell-mediated cytotoxicity activity and cetuximab response in KRAS wild-type metastatic colorectal cancer patients.World journal of gastrointestinal oncology · 2016Article
- PRMT1-mediated methylation of the EGF receptor regulates signaling and cetuximab response.The Journal of clinical investigation · 2015Article
- Immunological visibility: posttranscriptional regulation of human NKG2D ligands by the EGF receptor pathway.Science translational medicine · 2014Article
- Immunomic, genomic and transcriptomic characterization of CT26 colorectal carcinoma.BMC genomics · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Epidermal growth factor receptor (EGFR)-targeting therapeutics have shown efficacy in the treatment of colorectal cancer patients. Clinical studies have revealed that activating mutations in the KRAS protooncogene predict resistance to EGFR-targeted therapy. However, the causality between mutant KRAS and resistance to EGFR inhibition has so far not been demonstrated. Here, we show that deletion of the oncogenic KRAS allele from colorectal tumor cells resensitizes those cells to EGFR inhibitors. Resensitization was accompanied by an acquired dependency on the EGFR for maintaining basal extracellular signal-regulated kinase (ERK) activity. Deletion of oncogenic KRAS not only resensitized tumor cells to EGFR inhibition but also promoted EGF-induced NRAS activation, ERK and AKT phosphorylation, and c-FOS transcription. The poor responsiveness of mutant KRAS tumor cells to EGFR inhibition and activation was accompanied by a reduced capacity of these cells to bind and internalize EGF and by a failure to retain EGFR at the plasma membrane. Of 16 human colorectal tumors with activating mutations in KRAS, 15 displayed loss of basolateral EGFR localization. Plasma membrane localization of the EGFR could be restored in vitro by suppressing receptor endocytosis through Rho kinase inhibition. This caused an EGFR-dependent increase in basal and EGF-stimulated ERK phosphorylation but failed to restore tumor cell sensitivity to EGFR inhibition. Our results demonstrate a causal role for oncogenic KRAS in desensitizing tumor cells not only to EGFR inhibitors but also to EGF itself.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.