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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Marshall, C. J. (1995) · Cell · doi:10.1016/0092-8674(95)90401-8 · Cited by 3,906
The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism
Engelman, J. A., Luo, J., & Cantley, L. C. (2006) · Nature Reviews Genetics · doi:10.1038/nrg1879 · Cited by 3,330
Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer
Roberts, P. J., & Der, C. J. (2007) · Oncogene · doi:10.1038/sj.onc.1210422 · Cited by 2,788
The ErbB signaling network: receptor heterodimerization in development and cancer
Olayioye, M. A., Neve, R. M., Lane, H. A., & Hynes, N. E. (2000) · The EMBO Journal · doi:10.1093/emboj/19.13.3159 · Cited by 2,489
Glycogen synthase kinase-3β regulates cyclin D1 proteolysis and subcellular localization
Diehl, J. A., Cheng, M., Roussel, M. F., & Sherr, C. J. (1998) · Genes & Development · doi:10.1101/gad.12.22.3499 · Cited by 2,130
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
Wellbrock, C., Karasarides, M., & Marais, R. (2004) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1498 · Cited by 1,223
Rodriguez‐Viciana, P., Warne, P. H., Khwaja, A., Marte, B. M., Pappin, D., Das, P., Waterfield, M. D., Ridley, A. J., & Downward, J. (1997) · Cell · doi:10.1016/s0092-8674(00)80226-3 · Cited by 1,060
Requirement for Ras in Raf activation is overcome by targeting Raf to the plasma membrane
Leevers, S. J., Paterson, H. F., & Marshall, C. J. (1994) · Nature · doi:10.1038/369411a0 · Cited by 1,011
Flagged first, then by citations
Cited by
Sorted by citations
Items 301–348 of 348
Targeted KRAS G12V degradation elicits efficient and durable lung adenocarcinoma regression in vivoPreprint
Martín, A. J. M., García-Pérez, I. M., José, S. S., Rojo, P., Riego‐Mejías, C., Teodósio, C., Barbosa, B. M. G., Sánchez, C., Folch-I-Casanovas, I., Caballol, A. O., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.12.13.627539 · Cited by 1
Dynamic and Biphasic Regulation of Cell Migration by RasPreprint
Lin, Y., Parajón, E., Yuan, Q., Ye, S., Qin, G., Deng, Y., Borleis, J. A., Koyfman, A., Iglesias, P. A., Κωνσταντόπουλος, Κ., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.02.13.638204 · Cited by 1
Preamble to Cytoplasmic Protein Kinases
Thiriet, M. (2012) · Biomathematical and biomechanical modeling of the circulatory and ventilatory systems · doi:10.1007/978-1-4614-4370-4_3
Discovery and restoration of aberrant nuclear structure and genome behaviour in breast cancer cells
Ahmed, M. H. (2013) · Brunel University Research Archive (BURA) (Brunel University London)
An ependymal cell quest : identification and functional role of spinal cord neural stem cells
Sabelström, H. (2014) · Figshare
Porquet, M. Z. (2010) · LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas)
Ras in epidermal proliferation
Drosten, M., Lechuga, C. G., & Barbacid, M. (2014) · Oncotarget · doi:10.18632/oncotarget.2275
Self-citationGenes and signaling pathways affecting the pathogenesis of melanoma
Varughese, B. E., & Tarapore, R. S. (2013) · Postdoc Journal · doi:10.14304/surya.jpr.v1n2.4
Updating the Mammalian Cell Cycle: The Role of Interphase Cdks in Tissue Homeostasis and Cancer
Barbacid, M. (2010) · Research and perspectives in Alzheimer's disease · doi:10.1007/978-3-642-16602-0_1
Self-citationCytosolic Protein Phosphatases
Thiriet, M. (2012) · Biomathematical and biomechanical modeling of the circulatory and ventilatory systems · doi:10.1007/978-1-4614-4370-4_8
Other Major Types of Signaling Mediators
Thiriet, M. (2012) · Biomathematical and biomechanical modeling of the circulatory and ventilatory systems · doi:10.1007/978-1-4614-4370-4_10
Towards functional multiscale analysis of colorectal cancer
Briffa, R. (2014) · ERA
Mechanical modification of dental implants to control bone retention
Alexander, H., & Ricci, J. (2016) · Elsevier eBooks · doi:10.1016/b978-0-08-100287-2.00002-1
[Should heart surgery and thromboendarterectomy of the carotid artery be done simultaneously?].
Christenson, J. T., Maurice, J., Simonet, F., Velebit, V., & Schmuziger, M. (1996) · PubMed
Albeck, J. G., Gillies, T. E., Blizard, H., & Pargett, M. (2017)
Hart, M. R. (2013) · UA Campus Repository (The University of Arizona)
Role of HRas and NRas in murine lung development and neonatal survival
Fuentes‐Mateos, R. (2021) · Gredos (University of Salamanca) · doi:10.14201/gredos.148393
Thiriet, M. (2012) · Biomathematical and biomechanical modeling of the circulatory and ventilatory systems · doi:10.1007/978-1-4614-4370-4_11
PKC-alpha promotes phosphorylation of KRAS suppressing its oncogenic propertiesPreprint
Joglekar, T., Ku, A., Schollaert, E., Gong, Y., Stewart-Ornstein, J., Urisman, A., & Wang, M.-T. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.05.24.493257
Chen, S., Vedula, R. S., Cuevas-Navarro, A., Lü, B., Hogg, S. J., Wang, E., Benbarche, S., Knorr, K. L. B., Kim, W. J., Stanley, R. F., et al. (2023) · doi:10.1158/2159-8290.c.6549783
Caspase 8 protects pancreatic neoplasia from KRAS-driven necroptotic primingPreprint
Tishina, S., Dahlhaus, A., Androulidaki, A., Kotliar, M., Mulalic, L., Rakhsh-Khorshid, H., Hocher, F., Stroh, J., Beck, J., Manik, M., et al. (2023) · Research Square · doi:10.21203/rs.3.rs-2971504/v1
Oncogenic KRAS-induces necroptotic priming of pancreatic neoplasiaPreprint
Tishina, S., Dahlhaus, A., Androulidaki, A., Kotliar, M., Mulalic, L., Rakhsh-Khorshid, H., Hocher, F., Stroh, J., Beck, J., Manik, M., et al. (2023) · Research Square · doi:10.21203/rs.3.rs-2971504/v2
Laranjeira, A. C., Berger, S., Kohlbrenner, T., Greter, N. R., & Hajnal, A. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.10.12.562015
Unraveling the Significance of Mg2+ Dependency and Nucleotide Binding Specificity of H-RAS
Tagad, A., & Patwari, G. N. (2024) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.3c06998
Quality Control of an Isogenic H/N/KRAS-Less Mouse Embryonic Fibroblast Cell Line Panel
Xu, B., & Powell, K. (2024) · Methods in molecular biology · doi:10.1007/978-1-0716-3822-4_24
Kaczmarczyk, J. A., Whiteley, G., & Blonder, J. (2024) · Methods in molecular biology · doi:10.1007/978-1-0716-3922-1_17
Ai, Y., Ding, Q., Wan, Z., Tyagi, S., Indeglia, A., Murphy, M. E., & Tian, B. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.09.26.613909
The Noncanonical RAS/MAPK Pathway and the RASopathies
Mo, S., & Castel, P. (2024) · Springer eBooks · doi:10.1007/978-3-031-62945-7_19
Mondal, J., Lam, D., Gerritsen, M. E., Brotz, T. M., Kennedy, J. G., Rehlaender, B., Ross, A. J., Levy, D. E., Bonagura, C. A., Lanzilotta, W. N., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.03.28.645837
Deciphering Novel Molecular Targets in Neuro-Oncology: An Update
Raja, K. A., Sakthivel, K. M., Prabhu, V. V., Muthukrishnan, S., Sundaram, P., Saravanan, M., & Rasmi, R. R. (2025) · Journal of Environmental Pathology Toxicology and Oncology · doi:10.1615/jenvironpatholtoxicoloncol.2025059098
The employment of double-adjuvant nanoparticle to enhance immune responses for neoantigen vaccine
Xiao, L., Wu, Y., Dai, Y., Sun, Y., & Chen, S. (2025) · Nano Research · doi:10.26599/nr.2025.94907712
Yasmeen, Karhana, S., Baboota, S., Khan, M. A., & Ali, J. (2025) · Assay and Drug Development Technologies · doi:10.1089/adt.2024.083
The role of p19 C-H-Ras protein in metastasis and proliferative pathways
Cruz, G. D., & Marlen, R. (2013) · LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas)
Mlakar, V., Morel, E., Mlakar, S. J., Ansari, M., & Gumy‐Pause, F. (2021) · Figshare · doi:10.6084/m9.figshare.14752291
MAPK pathway modulation and its implications in KRAS mutant lung adenocarcinoma
Román, S. D. H. (2023) · theses.fr (ABES) · doi:10.70675/8eaccae1ze96bz4279zb69fzaafa5e50c341
Oncogenic KRAS-driven type I interferon signalling primes pancreatic cancer for necroptosis
Tishina, S., Dahlhaus, A., Manik, M., Mulalic, L., Murr, J., Kotliar, M., Rakhsh-Khorshid, H., Kostopoulou, M., Hocher, F., Stroh, J., et al. (2026) · Nature Communications · doi:10.1038/s41467-026-73189-8 · Cited by 1
KRAS G12C and KRAS G12D respond to lipid metabolism in an allele-specific manner
Arora, N., Liang, H., Kattan, W. E., Yao, W., Ying, H., Liu, J., & Zhou, Y. (2026) · Journal of Lipid Research · doi:10.1016/j.jlr.2026.101079 · Cited by 3
Londoño, C. J., & Zheng, B. (2026) · Cells · doi:10.3390/cells15131135 · Cited by 1
Lipidation as a Driver of Spatial Organization and Function in Proteins and Nucleic Acids
Zhang, H., & Izgü, E. Ç. (2026) · ACS Chemical Biology · doi:10.1021/acschembio.6c00528
HRAS promotes mutant NRAS–driven transformation with codon and allele specificity
Lee, H., Hughes, J. M., LaMorte, J. P., Finniff, B. A., Binette, P., Gunasekara, S. K., Covas, A., Wall, V. E., Esposito, D., Wilkerson, M. D., et al. (2026) · Science Signaling · doi:10.1126/scisignal.aej6209
Atchison, B., Byars, S., Prestes, P. R., Myers, M. A., Wang, Y., & Charchar, F. J. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27188195
Coma, S., Musteanu, M., Malvezzi, C. C., Jamieson, R., Patrucco, E., Mira, A., Dilly, J., Li, Z., Fernández‐Rodríguez, A., López-García, A., et al. (2026) · Science Translational Medicine · doi:10.1126/scitranslmed.aea4608
Self-citation
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
