The DOI matches its Crossref record; 60 of the 60 references it cites were found in a registry or an index.
Genetic analysis of Ras signalling pathways in cell proliferation, migration and survival
Open accessAbstract
We have used mouse embryonic fibroblasts (MEFs) devoid of Ras proteins to illustrate that they are essential for proliferation and migration, but not for survival, at least in these cells. These properties are unique to the Ras subfamily of proteins because ectopic expression of other Ras-like small GTPases, even when constitutively active, could not compensate for the absence of Ras proteins. Only constitutive activation of components of the Raf/Mek/Erk pathway was sufficient to sustain normal proliferation and migration of MEFs devoid of Ras proteins. Activation of the phosphatidylinositol 3-kinase (PI3K)/PTEN/Akt and Ral guanine exchange factor (RalGEF)/Ral pathways, either alone or in combination, failed to induce proliferation or migration of Rasless cells, although they cooperated with Raf/Mek/Erk signalling to reproduce the full response mediated by Ras signalling. In contrast to current hypotheses, Ras signalling did not induce proliferation by inducing expression of D-type Cyclins. Rasless MEFs had normal levels of Cyclin D1/Cdk4 and Cyclin E/Cdk2. However, these complexes were inactive. Inactivation of the pocket proteins or knock down of pRb relieved MEFs from their dependence on Ras signalling to proliferate.
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“the ablation of all RAS isoform expression causes death of adult mice within a few weeks of induction (60, 61).”
From Expanding the Reach of Precision Oncology by Drugging All KRAS Mutants (2022) · cites this paper as [60]
In the citing paper
“The activated state of KRAS accumulating in vivo results in the activation of downstream signaling pathways and is associated with tumorigenesis, aggressive disease, and poor prognosis [14, 15].”
From Targeting KRAS mutant cancers: from druggable therapy to drug resistance (2022) · cites this paper as [15]
In the citing paper
“The activated state of KRAS accumulating in vivo results in the activation of downstream signaling pathways and is associated with tumorigenesis, aggressive disease, and poor prognosis [14, 15].”
From Targeting KRAS mutant cancers: from druggable therapy to drug resistance (2022) · cites this paper as [15]
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Cites
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RAS oncogenes: the first 30 years
Malumbres, M., & Barbacid, M. (2003) · Nature Reviews Cancer · doi:10.1038/nrc1097 · Cited by 1,902 · cited 1×
“These studies have illustrated how Ras proteins become activated by growth factor receptors and have unveiled those pathways implicated in mediating downstream signalling to their ultimate effectors (reviewed in Malumbres and Barbacid, 2003).”
BackgroundSelf-citationBeyond PTEN mutations: the PI3K pathway as an integrator of multiple inputs during tumorigenesis
Cully, M., You, H., Levine, A. J., & Mak, T. W. (2006) · Nature reviews. Cancer · doi:10.1038/nrc1819 · Cited by 1,267
The RAF proteins take centre stage
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A Pericyte Origin of Spinal Cord Scar Tissue
Göritz, C., Dias, D. O., Tomilin, N., Barbacid, M., Shupliakov, O., & Frisén, J. (2011) · Science · doi:10.1126/science.1203165 · Cited by 858
Self-citationDirect small-molecule inhibitors of KRAS: from structural insights to mechanism-based design
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Metadata
- Authors
- Drosten, M., Dhawahir, A., Sum, E. Y. M., Urosevic, J., Lechuga, C. G., Esteban, L. M., Castellano, E., Guerra, C., Santos, E., & Barbacid, M.
- Affiliations
- Spanish National Cancer Research Centre (ES)
- Universidad de Salamanca (ES)
- Corresponding author
- Barbacid, Mariano
- ORCID
- Venue
- The EMBO Journal
- Published
- 2010-02-11
- Volume
- 29
- Issue
- 6
- Pages
- 1091-1104
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC2845279
- OpenAlex
- W2113609800
- Cited by
- 347
- References
- 60
- Citations by year
- 2026: 19 · 2025: 24 · 2024: 33 · 2023: 22 · 2022: 35 · 2021: 38 · 2020: 23 · 2019: 13 · 2018: 23 · 2017: 21 · 2016: 11 · 2015: 15 · 2014: 9 · 2013: 17 · 2012: 25
- FWCI
- 7.81
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- The EMBO Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- Ras signaling, Ras proteins, cell proliferation, cell migration, cell survival, mouse embryonic fibroblasts, Raf/MEK/ERK pathway, PI3K/Akt signaling, cyclin D1/CDK4, cyclin E/CDK2, pocket proteins, retinoblastoma protein, cell cycle regulation
- MeSH terms
- Animals, Cell Movement, Cell Survival, Fibroblasts, Signal Transduction, ras Proteins, Phosphatidylinositol 3-Kinases, Extracellular Signal-Regulated MAP Kinases, raf Kinases, Cell Proliferation, Mice
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