ArticleCancer discovery2013
Oncogenic and wild-type Ras play divergent roles in the regulation of mitogen-activated protein kinase signaling.
Article in Cancer discovery, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 132 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
132 citing papers in PubMed, 1 synthesis or guideline pooled it, 213 citations in OpenAlex.
- Unraveling the Genetic Web: H-Ras Expression and Mutation in Oral Squamous Cell Carcinoma-A Systematic Review.Head and neck pathology · 2024Pooled it
- Trial
- HRAS promotes mutant NRAS-driven transformation with codon and allele specificity.Science signaling · 2026Article
- A high-MAPK, low-WNT cell state drives metastatic dissemination in colorectal cancer.Nature cancer · 2026Article
- Mutant and Wild-Type RAS Cross-talk and Stoichiometric Deficiencies Are Determinants of Sensitivity to Targeted Therapies in KRASG12R Pancreatic Ductal Adenocarcinoma.Cancer research · 2026Article
- Targeting cancer expressed EGFR with a humanized monoclonal antibody.Scientific reports · 2026Article
- SOS1: tracking the evolving path from promising to actionable therapeutic target in RAS-dependent cancers.Molecular cancer · 2026Review
- Article
- Secretory carrier membrane protein 3 modulates nuclear ERK1/2 signaling and drug response in triple-negative breast cancer.Frontiers in oncology · 2026Article
- Non-canonical EGFR signaling promotes MAPK-dependent extrusion of epithelial cells.Journal of cell science · 2025Article
- Wild-type RAS signaling is an essential therapeutic target inScience signaling · 2025Article
- Review
- Proto-Oncogene HRAS Transcript Level and Overall Survival in Stages II and III Colorectal Cancer.Cancer medicine · 2025Article
- Inhibition and degradation of NRAS with a pan-NRAS monobody.Oncogene · 2024Article
- Adaptor protein Abelson interactor 1 in homeostasis and disease.Cell communication and signaling : CCS · 2024Review
- Farnesyl-transferase inhibitors show synergistic anticancer effects in combination with novel KRAS-G12C inhibitors.British journal of cancer · 2024Article
- CRISPR-mediated reversion of oncogenic KRAS mutation results in increased proliferation and reveals independent roles of Ras and mTORC2 in the migration of A549 lung cancer cells.Molecular biology of the cell · 2023Article
- A Nonconserved Histidine Residue on KRAS Drives Paralog Selectivity of the KRASG12D Inhibitor MRTX1133.Cancer research · 2023Article
- Hematopoietic progenitor kinase 1 inhibits the development and progression of pancreatic intraepithelial neoplasia.The Journal of clinical investigation · 2023Article
- Negative correlation between acetyl-CoA acyltransferase 2 and cetuximab resistance in colorectal cancer.Acta biochimica et biophysica Sinica · 2023Article
72 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
unlabelledH-Ras, K-Ras, and N-Ras regulate cellular growth and survival and are often activated by somatic mutation in human tumors. Although oncogenic lesions occur in a single Ras isoform within individual tumors, it is unclear whether the remaining wild-type isoforms play supporting roles in tumor growth. Here, we show that oncogenic and wild-type Ras isoforms play independent and nonredundant roles within the cell. Oncogenic Ras regulates basal effector pathway signaling, whereas wild-type Ras mediates signaling downstream of activated receptor tyrosine kinases (RTK). We show that both are necessary for exponential growth of Ras-mutant cell lines. Furthermore, we show that oncogenic Ras desensitizes signaling from EGF receptor (EGFR). Depletion of oncogenic Ras with siRNA oligonucleotides relieves this negative feedback, leading to the hyperactivation of EGFR and wild-type Ras signaling. Consistent with this model, combining oncogenic Ras depletion with EGFR inhibition potently increases cell death. SIGNIFICANCE: The results of this study highlight a novel role for wild-type Ras signaling in cancer cells harboring oncogenic RAS mutations. Furthermore, these findings reveal that therapeutically targeting oncogenic Ras signaling alone may be ineffective owing to feedback activation of RTKs, and suggest that blocking upstream RTKs in combination with downstream effector pathways may be beneficial in the treatment of Ras-mutant tumors.
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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.