The DOI matches its Crossref record; 122 of the 122 references it cites were found in a registry or an index.
RAS oncogenes: the first 30 years
Abstract
From the pioneering work with acute transforming retroviruses to the current post-genomic era, RAS genes have always been at the leading edge of signal transduction and molecular oncology. Yet, a complete understanding of RAS function and dysfunction - mainly in human cancer - is still to come. The knowledge that has accumulated since their discovery 30 years ago has, however, been remarkable, and should pave the way for not only solving the outstanding issues regarding RAS biology, but also for developing efficacious drugs that could have a significant impact on cancer treatment.
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“On the other hand, the KRAS proteins are featureless. They have a nearly spherical structure that lacks a deep hydrophobic pocket and has no obvious binding site [20].”
From Targeting KRAS mutant cancers: from druggable therapy to drug resistance (2022) · cites this paper as [20]
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Morales, E., Porta, M. S., Vioqué, J., López‐Jiménez, T., Mendez, M. A., Pumarega, J. A., Malats, N., Crous‐Bou, M., Ngo, J., Rifà, J., et al. (2007) · Journal of Epidemiology & Community Health · doi:10.1136/jech.2007.060632 · Cited by 31
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“To this end, oncogenic KRAS-driven lung tumour models will be useful since the progression of early precursor lesions into malignant adenocarcinoma can be tracked in these models (Jackson et al , 2001; Mainardi et al , 2014).”
InfluentialRasopatías: trastornos del desarrollo con predisposición al cáncer y manifestaciones cutáneas
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Sonic Hedgehog Signaling in Thyroid Cancer
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Perspectives of RAS and RHEB GTPase Signaling Pathways in Regenerating Brain Neurons
Schöneborn, H., Raudzus, F., Coppey, M., Neumann, S., & Heumann, R. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19124052 · Cited by 32
“RAS is not only capable of activating cellular transcription, translation, cell-cycle progression, and survival but also apoptosis suggesting that the physiological outcome of RAS activation depends on the cellular context and cell type [5,16].”
BackgroundGenetic syndromes with vascular malformations – update on molecular background and diagnostics
Ustaszewski, A., Janowska-Głowacka, J., Wołyńska, K., Pietrzak, A., & Badura‐Stronka, M. (2020) · Archives of Medical Science · doi:10.5114/aoms.2020.93260 · Cited by 30
The Emerging Role of Ras Pathway Signaling in Pediatric Cancer
Ney, G. M., McKay, L. M., Koschmann, C. J., Mody, R. J., & Li, Q. (2020) · Cancer Research · doi:10.1158/0008-5472.can-20-0916 · Cited by 32
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Shen, M., Qi, R., Ren, J., Lv, D., & Yang, H. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2021.780655 · Cited by 31
Ramalingam, P. S., Balakrishnan, P., Rajendran, S., Jothi, A., Rajasekaran, R., & Arumugam, S. (2023) · Current Issues in Molecular Biology · doi:10.3390/cimb45030137 · Cited by 32
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“The KRAS gene encodes KRAS, a member of the RAS family of guanosine triphosphate (GTP) hydrolases (GTPases), which is the human cellular homologue of the Kirsten rat sarcoma virus.(20,21) RAS proteins, including KRAS, are intracellular signaling molecules that cycle between an active GTP-bound and an inactive guanosin…”
BackgroundContext-dependent roles of mutant B-Raf signaling in melanoma and colorectal carcinoma cell growth
Hao, H., Muniz-Medina, V. M., Mehta, H., Thomas, N. E., Khazak, V., Der, C. J., & Shields, J. M. (2007) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-06-0728 · Cited by 30
“Mutational activation of Ras (H-Ras, K-Ras, and N-Ras) is associated with a diverse spectrum of human cancers (1).”
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LoRusso, P. M., Schalper, K. A., & Sosman, J. A. (2019) · Pigment Cell & Melanoma Research · doi:10.1111/pcmr.12847 · Cited by 30
“Under normal conditions, NRAS relies on signaling from activated receptor tyrosine kinases to drive downstream signaling through the MAPK and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathways (Malumbres & Barbacid, 2003).”
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Dissecting the Senescence-like Program in Tumor Cells Activated by Ras Signaling
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Dai, H., Zhao, K., Zhao, Y., Jiang, K., Hang, Z., Huang, X., Luo, W., Nie, J., Qin, C., & Zhou, W. (2025) · BMC Urology · doi:10.1186/s12894-025-01914-4 · Cited by 29
“The RAS gene family (HRAS, NRAS, KRAS) [37], a classical oncogenic driver, has been implicated in promoting tumor proliferation and metastasis [38].”
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Chen, J., Shen, Q. “., Labow, M., & Gaither, L. A. (2011) · Cancer Research · doi:10.1158/0008-5472.can-10-3761 · Cited by 29
“Although the RAS oncogene has been studied for more than 3 decades, there is no drug on the market that sufficiently inhibits RAS, despite extensive efforts to inhibit activated RAS with low molecular weight inhibitors (3, 8).”
BackgroundInhibition of prenylated KRAS in a lipid environment
Jansen, J. M., Wartchow, C. A., Jahnke, W., Fong, S. K., Tsang, T., Pfister, K. B., Zavorotinskaya, T., Bussiere, D. E., Cheng, J. M., Crawford, K. R., et al. (2017) · PLoS ONE · doi:10.1371/journal.pone.0174706 · Cited by 29
“It has been known since the 1980’s that RAS mutations are the driver in about 30% of cancers with high prevalence in carcinomas of the pancreas, colon, and lung [9, 10].”
Pattanayak, R., Barua, A., Das, A. K., Chatterjee, T., Pathak, A., Choudhury, P., Sen, S., Saha, P., & Bhattacharyya, M. (2018) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2018.09.011 · Cited by 29
RetractedThe Insulin-like Growth Factor System and Colorectal Cancer
Gligorijević, N., Dobrijević, Z., Šunderić, M., Robajac, D., Četić, D., Penezić, A., Miljuš, G., & Nedić, O. (2022) · Life · doi:10.3390/life12081274 · Cited by 30
Biomarkers in Metastatic Colorectal Cancer: Status Quo and Future Perspective
Puccini, A., Seeber, A., & Berger, M. D. (2022) · Cancers · doi:10.3390/cancers14194828 · Cited by 31
“The RAS family is one of the most frequently mutated genes across all malignancies, including CRC [75], and functions as regulators of the intracellular signaling transduction cascades involved in cell growth, differentiation and survival [76].”
BackgroundPredictive and Prognostic Markers in the Treatment of Metastatic Colorectal Cancer (mCRC)
Stintzing, S., Stremitzer, S., Sebio, A., & Lenz, H. (2014) · Hematology/Oncology Clinics of North America · doi:10.1016/j.hoc.2014.09.009 · Cited by 29
Compartmentalized Ras signaling differentially contributes to phenotypic outputs
Aran, V., & Prior, I. A. (2013) · Cellular Signalling · doi:10.1016/j.cellsig.2013.05.004 · Cited by 28
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“Several studies have demonstrated that forced expression of H-Ras induces cellular senescence even though activated Ras can cause malignant transformation [44,45,46,47,48,49,50].”
BackgroundMutationally activated K-ras 4A and 4B both mediate lung carcinogenesis
Patek, C. E., Arends, M. J., Wallace, W. A., Luo, F., Hagan, S., Brownstein, D. G., Rose, L., Devenney, P. S., Walker, M., Plowman, S. J., et al. (2007) · Experimental Cell Research · doi:10.1016/j.yexcr.2007.11.004 · Cited by 29
Khan, S. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i11.2979 · Cited by 29
Biological Approaches to Therapy of Pancreatic Cancer
Wong, H. H., & Lemoine, N. R. (2008) · Pancreatology · doi:10.1159/000151536 · Cited by 29
“The gene encodes a 21-kDa membrane-bound guanosine triphosphate (GTP)-binding protein involved in growth factor-mediated signal transduction pathways. It can be activated through the overexpression or activation of ras-activating signalling partners, such as the epidermal growth factor receptor (EGFR). The best-charac…”
Let-7 Sensitizes KRAS Mutant Tumor Cells to Chemotherapy
Dai, X., Jiang, Y., & Tan, C. (2015) · PLoS ONE · doi:10.1371/journal.pone.0126653 · Cited by 29
“KRASmutations occur in approximately 20% of all human cancers and are particularly prevalent in pancreatic ductal adenocarcinoma (PDAC, ~90%), non-small cell lung cancer (NSCLC, ~25%) and colorectal cancer (~40%) [1].”
BackgroundStricker, T. P., & KUMAR, V. (2010) · Elsevier eBooks · doi:10.1016/b978-1-4377-0792-2.50012-2 · Cited by 28
Lifetime History of Tobacco Consumption and K-ras Mutations in Exocrine Pancreatic Cancer
Crous‐Bou, M., Porta, M. S., López‐Jiménez, T., Jariod, M., Malats, N., Alguacil, J., Morales, E., Fernández, E., Corominas, J. M., Carrato, A., et al. (2007) · Pancreas · doi:10.1097/mpa.0b013e31805d8fa4 · Cited by 29
“In animal models, benzopyrene, other polycyclic aromatic hydrocarbons, and other tobacco carcinogens (that are not nitrosamines) cause K-ras mutations in several tumors (eg, in lung cancer), but not in pancreatic tumors.(10,29,48,49) Moreover, pancreatic tissue is not a target organ for these carcinogens, whereas they…”
BackgroundSlowing Down the Ras Lane: miRNAs as Tumor Suppressors?
Morris, J. P., & McManus, M. T. (2005) · Science s STKE · doi:10.1126/stke.2972005pe41 · Cited by 28
Tardito, S., Matis, S., Zocchi, M. R., Benelli, R., & Poggi, A. D. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25137131 · Cited by 30
“KRAS is the main target of mutations (40% CRC), preferentially hitting codons 12 and 13 in exon 2 [77].”
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“Activation of ras oncogenes is implicated in human carcinogenesis [10], mainly by promoting cellular proliferation and inhibiting apoptosis [11].”
Yeh, H.-H., Tseng, Y.-F., Hsu, Y.-C., Lan, S., Wu, S., Raghavaraju, G., Cheng, D.-E., Lee, Y., Chang, T., Chow, N.-H., et al. (2015) · BMC Cancer · doi:10.1186/s12885-015-1155-7 · Cited by 28
“About 30% of human tumors express Ras point mutations [2].”
BackgroundKRAS mutational concordance between primary and metastatic colorectal adenocarcinoma
Paliogiannis, P., Cossu, A., Tanda, F., Palmieri, G., & Palomba, G. (2014) · Oncology Letters · doi:10.3892/ol.2014.2411 · Cited by 27
Regulation of RasGRP1 Function in T Cell Development and Activation by Its Unique Tail Domain
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“Moreover, RasGRP1 is one potential protein whose structural mutation or deregulated expression could mimic oncogenic Ras mutations [19], which are detected in many solid tumors and a subset of T lymphocytic leukemia [20,21,22].”
Profiling of a panel of radioresistant prostate cancer cells identifies deregulation of key miRNAs
McDermott, N., Meunier, A., Wong, S. C. K., Buchete, N., & Marignol, L. H. (2017) · Clinical and Translational Radiation Oncology · doi:10.1016/j.ctro.2017.01.005 · Cited by 28
Zhang, F., & Cao, H. (2018) · International Journal of Oncology · doi:10.3892/ijo.2018.4655 · Cited by 28
Anti-EGFR Therapy to Treat Metastatic Colorectal Cancer: Not for All
Martins, M., Mansinho, A., Cruz-Duarte, R., Lobo-Martins, S., & Costa, L. (2018) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-02771-1_8 · Cited by 26
KRAS regulation by small non-coding RNAs and SNARE proteins
Che, Y., Siprashvili, Z., Kovalski, J. R., Jiang, T., Wozniak, G. G., Elcavage, L. E., & Khavari, P. A. (2019) · Nature Communications · doi:10.1038/s41467-019-13106-4 · Cited by 30
“Following paraffin-embedding and sectioning, antigen retrieval was performed as follows: (1) Two washes in xylene (5 min each) (2) Two washes in 100% ethanol (5 min each) (3) Two washes in 95% ethanol (5 min each) (4) Two washes in 70% ethanol (5 min each) (5) Two washes in dH2O ethanol (5 min each) (6) Slides brought…”
MethodFrom basic researches to new achievements in therapeutic strategies of KRAS-driven cancers
Saliani, M., Jalal, R., & Ahmadian, M. R. (2019) · Cancer Biology and Medicine · doi:10.20892/j.issn.2095-3941.2018.0530 · Cited by 27
A review on the role of fatty acids in colorectal cancer progression
Hoxha, M., & Zappacosta, B. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.1032806 · Cited by 29
“Data have reported that around 40% of colon cancers have a KRAS mutation, which are associated with a higher tumor aggressiveness (Malumbres and Barbacid, 2003).”
BackgroundThe use of genetically modified mice in cancer risk assessment: Challenges and limitations
Eastmond, D. A., Vulimiri, S. V., French, J. E., & Sonawane, B. R. (2013) · Critical Reviews in Toxicology · doi:10.3109/10408444.2013.822844 · Cited by 28
“This is not surprising as the two most common genes targeted in the GM models, RAS and TP53, are master regulatory genes that control and/or influence many other genes and pathways within the cell (Malumbres & Barbacid, 2003; Menendez et al., 2009; Pylayeva-Gupta et al., 2011).”
BackgroundImportance of Domain Closure for the Autoactivation of ERK2
Barr, D. A., Oashi, T., Burkhard, K. A., Lucius, S., Samadani, R., Zhang, J., Shapiro, P., MacKerell, A. D., & van der Vaart, A. (2011) · Biochemistry · doi:10.1021/bi200503a · Cited by 28
CaM interaction and Ser181 phosphorylation as new K-Ras signaling modulators
Alvarez-Moya, B., Barceló, C., Tebar, F., Jaumot, M., & Agell, N. (2011) · Small GTPases · doi:10.4161/sgtp.2.2.15555 · Cited by 28
p120RasGAP-Mediated Activation of c-Src Is Critical for Oncogenic Ras to Induce Tumor Invasion
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“GTP-bound Ras regulates a complex signaling network by binding to and activating diverse classes of effector molecules, such as Raf, phosphatidylinositol 3-kinase (PI3K), and RalGEFs (3).”
BackgroundPancreatic cancer: Promise for personalised medicine?
Braat, H., Bruno, M. J., Kuipers, E. J., & Peppelenbosch, M. P. (2011) · Cancer Letters · doi:10.1016/j.canlet.2011.11.034 · Cited by 27
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“The ras family of proteins are ubiquitous small GTPases, which play an important role in cellular signal transduction (1).”
BackgroundVillagómez, F. R., Contreras, O. M., Cerna-Cortés, J. F., & Patiño‐López, G. (2018) · Small GTPases · doi:10.1080/21541248.2018.1463895 · Cited by 29
“The focus on Ras allowed the discovery of the Ras superfamily, a group of related proteins comprising different subfamilies: RhoGTPases, ArfGTPases, RanGTPases, RasGTPases, and RabGTPases [1,3].”
BackgroundInfluentialCapicua suppresses colorectal cancer progression via repression of ETV4 expression
Lee, J.-S., Kim, E., Lee, J., Kim, D., Kim, H., Kim, C.-J., Kim, S., Jeong, D., & Lee, Y. (2020) · Cancer Cell International · doi:10.1186/s12935-020-1111-8 · Cited by 30
New druggable targets in the Ras pathway?
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Buchmann, A., Karcier, Z., Schmid, B., Strathmann, J., & Schwarz, M. (2007) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2007.08.015 · Cited by 28
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Localization, Not Important in All Tumor-Suppressing Properties: A Lesson Learnt from Scribble
Elsum, I. A., & Humbert, P. O. (2013) · Cells Tissues Organs · doi:10.1159/000348423 · Cited by 27
PIM1 kinase and its diverse substrate in solid tumors
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“One specific target that has been extensively researched in PDAC is the oncoprotein K-Ras, which is found to be mutated in over 90% of PDAC cases [67].”
BackgroundGenomic alterations in pancreatic cancer and their relevance to therapy
Takai, E., & Yachida, S. (2015) · World Journal of Gastrointestinal Oncology · doi:10.4251/wjgo.v7.i10.250 · Cited by 27
Low RASSF6 expression in pancreatic ductal adenocarcinoma is associated with poor survival
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Huang, Z., Liu, M., Li, D., Tan, Y., Zhang, R., Xia, Z., Wang, P., Jiao, B., Liu, P., & Ren, R. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.011060 · Cited by 27
“RAS proteins are small GTPases that regulate diverse cellular processes, including proliferation, differentiation, migration, apoptosis, and senescence (1).”
BackgroundUnderstand KRAS and the Quest for Anti-Cancer Drugs
Han, C. W., Jeong, M. S., & Jang, S. B. (2021) · Cells · doi:10.3390/cells10040842 · Cited by 27
“Normally, the cycling of RAS protein by GTPases is tightly regulated by the binding of guanosine triphosphate (GTP) to nucleotide exchange factors (GEFs) and by the hydrolysis of GTP to guanosine diphosphate (GDP) by GTPase activating proteins (GAPs) [1,2].”
BackgroundReal-time in vitro measurement of GTP hydrolysis
Shutes, A., & Der, C. J. (2005) · Methods · doi:10.1016/j.ymeth.2005.05.019 · Cited by 27
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Selimoglu‐Buet, D., Gallais, I., Lauret, E., Denis, N., Lombard, B., Guillonneau, F., Kosmider, O., Loew, D., Dusanter‐Fourt, I., Guillouf, C., et al. (2012) · Blood · doi:10.1182/blood-2011-07-368316 · Cited by 28
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Prognostic Role of KRAS mRNA Expression in Breast Cancer
Hwang, K., Kim, B. H., Oh, S., Park, S. Y., Jung, J., Kim, J.-J., Choi, I. S., Jeon, S. Y., & Kim, W. (2019) · Journal of Breast Cancer · doi:10.4048/jbc.2019.22.e55 · Cited by 27
“It was the first report in the history of RAS research [18,19].”
BackgroundTherapeutic targeting of protein S-acylation for the treatment of disease
Fraser, N. J., Howie, J., Wypijewski, K. J., & Fuller, W. (2019) · Biochemical Society Transactions · doi:10.1042/bst20190707 · Cited by 29
“Case study 1: Oncogenic Ras Ras proteins function as molecular switches transmitting signals from cell surface growth factor receptors to intracellular effector proteins cycling between inactive (GDP bound) and active (GTP) states [50, 51].”
BackgroundRamalingam, P. S., Priyadharshini, A., Emerson, I. A., & Arumugam, S. (2023) · Frontiers in Medicine · doi:10.3389/fmed.2023.1107128 · Cited by 25
Tedeschi, A., Schischlik, F., Rocchetti, F., Popow, J., Ebner, F., Gerlach, D., Geyer, A., Santoro, V., Boghossian, A. S., Rees, M. G., et al. (2024) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-24-0386 · Cited by 28
“KRAS is a small GTPase acting as a molecular switch driving intracellular proliferation and survival pathways (5, 6).”
Physiological Analysis of Oncogenic K‐Ras
Pérez-Mancera, P. A., & Tuveson, D. A. (2006) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(05)07053-9 · Cited by 26
Clinical relevance of KRAS mutations in codon 13: Where are we?
Er, T., Chen, C.-C., Bujanda, L., & Herreros‐Villanueva, M. (2013) · Cancer Letters · doi:10.1016/j.canlet.2013.09.012 · Cited by 26
“The incorporation of other amino acids, most usually aspartate and valine at codon 12 and aspartate at codon 13 [19], brings about the projection of larger amino acid side chains into the GDP/GTP binding pocket of the protein, interfering with the steric hindrance in GTP hydrolysis [20].”
BackgroundModulation of E-cadherin expression by K-Ras; involvement of DNA methyltransferase-3b
Kwon, O., Jeong, S. J., Kim, S. O., He, L., Lee, H. G., Jang, K. L., Osada, H., Jung, M., Kim, B., & Ahn, J. S. (2010) · Carcinogenesis · doi:10.1093/carcin/bgq071 · Cited by 26
Extracellular signal-regulated kinase 1 and 2 in cancer therapy: a focus on hepatocellular carcinoma
Mehdizadeh, A., Somi, M. H., Darabi, M., & Jabbarpour-Bonyadi, M. (2016) · Molecular Biology Reports · doi:10.1007/s11033-016-3943-9 · Cited by 26
“In addition, Several studies have demonstrated that increased ERK cascade activity in HCC is not (or rarely) due to mutations in upstream proteins specially GTPase Ras and/or Raf protein kinase [28].”
Substrate Recognition of MARTX Ras/Rap1-Specific Endopeptidase
Biancucci, M., Rabideau, A. E., Lu, Z. M., Loftis, A. R., Pentelute, B. L., & Satchell, K. J. F. (2017) · Biochemistry · doi:10.1021/acs.biochem.7b00246 · Cited by 26
Ni, D., Liu, D., Zhang, J., & Lu, S. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19010151 · Cited by 26
Ras-Induced miR-146a and 193a Target Jmjd6 to Regulate Melanoma Progression
Anelli, V., Ordas, A., Kneitz, S., Muñoz‐Sagredo, L., Gourain, V., Schartl, M., Meijer, A. H., & Mione, M. (2018) · Frontiers in Genetics · doi:10.3389/fgene.2018.00675 · Cited by 26
“The oncogenic versions of the human RAS genes (KRAS, HRAS, and NRAS) have been the first and most successful drivers of cancer in transgenic mice (Chin et al., 1999a,b; Johnson et al., 2001; Malumbres and Barbacid, 2003).”
BackgroundOn The Role of Myelin and Lymphocyte Protein (MAL) In Cancer: A Puzzle With Two Faces
Lara‐Lemus, R. (2019) · Journal of Cancer · doi:10.7150/jca.30376 · Cited by 26
“Thus, in lymphocytes, the proliferative effect associated with MAL overexpression could at least in part be mediated by the Lck-signaling pathway (Ras-MAPK-mediated cell proliferation) [67]; transformed lymphocytes could have permanently activated this pathway and MAL overexpression could favor cell-transformation thr…”
BackgroundA perspective on the early days of RAS research
Weiss, R. A. (2020) · Cancer and Metastasis Reviews · doi:10.1007/s10555-020-09919-1 · Cited by 28
Molecular Biology and Therapeutic Perspectives for K-Ras Mutant Non-Small Cell Lung Cancers
Cekani, E., Epistolio, S., Dazio, G., Cefalì, M., Wannesson, L., Frattini, M., & Froesch, P. (2022) · Cancers · doi:10.3390/cancers14174103 · Cited by 27
“This group of genes is associated with the control of cell growth, survival and differentiation [1,2], and it is characterized by the most frequently observed genomic alterations in human cancers, being detected in approximately 19% of tumors [3,4].”
BackgroundA Review of Biomarkers and Their Clinical Impact in Resected Early-Stage Non-Small-Cell Lung Cancer
Cao, W., Tang, Q., Zeng, J., Jin, X., Zu, L., & Xu, S. (2023) · Cancers · doi:10.3390/cancers15184561 · Cited by 28
“KRAS, belonging to the RAS gene family, is activated by binding to GTP and triggers many cellular activation processes, including transcription, translation, cell survival, and apoptosis [61].”
BackgroundRAB7 counteracts PI3K-driven macropinocytosis activated at early stages of melanoma development
Alonso‐Curbelo, D., Osterloh, L., Cañón, E., Calvo, T. G., Martínez-Herranz, R., Karras, P., Martı́nez, S., Riveiro‐Falkenbach, E., Romero, P. L. O., Rodríguez‐Peralto, J. L., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.4055 · Cited by 26
“To this end, fresh preparations of primary melanocytes were transduced with lentiviral vectors encoding for HRASG12V, here used as a prototypical tool to assess PI3K-associated stress response programs [43] (results with activated NRAS and BRAF are presented below).”
MethodActivation of K-RAS by co-mutation of codons 19 and 20 is transforming
Naguib, A., Wilson, C. H., Adams, D. J., & Arends, M. J. (2011) · Journal of Molecular Signaling · doi:10.1186/1750-2187-6-2 · Cited by 26
“The incorporation of other amino acids, most commonly aspartate and valine at codon 12 and aspartate at codon 13 [6], brings about projection of larger amino acid side chains into the GDP/GTP binding pocket of the protein, interfering with the geometry of the transition state in which GTP hydrolysis is catalysed [7].”
BackgroundAblation of BRaf Impairs Neuronal Differentiation in the Postnatal Hippocampus and Cerebellum
Pfeiffer, V., Götz, R., Xiang, C., Camarero, G., Braun, A., Zhang, Y., Blum, R., Heinsen, H., Nieswandt, B., & Rapp, U. R. (2013) · PLoS ONE · doi:10.1371/journal.pone.0058259 · Cited by 26
“Examples are frequent somatic mutations of KRAS codons 12 and 13 [5] in various types of cancers in endodermal organs”
Backgroundde Atauri, P., Benito, A., Vizán, P., Zanuy, M., Mangues, R., Marín, S., & Cascante, M. (2010) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2010.11.015 · Cited by 26
Sudhir, P., Chen, C., Kumari, M. P., Wang, M.-J., Tsou, C., Sung, T., Chen, C., & Chen, C. (2012) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m112.020875 · Cited by 26
“Activated RAS oncogenes are known to be involved in various biological processes that are relevant to cancer, including transcriptional and translational regulation, cell-cycle progression, cytoskeleton organization, apoptosis, survival, cell proliferation, adhesion, and motility (4).”
NORE1B Is a Putative Tumor Suppressor in Hepatocarcinogenesis and May Act via RASSF1A
Macheiner, D., Gauglhofer, C., Rodgarkia‐Dara, C., Grusch, M., Brachner, A., Bichler, C., Kandioler, D., Sutterlüty, H., Mikulits, W., Schulte‐Hermann, R., et al. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-2144 · Cited by 26
Barnoud, T., Donninger, H., & Clark, G. J. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.697557 · Cited by 26
“In experimental systems, activated forms of Ras can be powerfully transforming, and transgenic animal models have validated the role of Ras activation in tumorigenesis (2, 3).”
BackgroundThe ability of endogenous Nras oncogenes to initiate leukemia is codon-dependent
Kong, G., Chang, Y.-I., You, X., Ranheim, E. A., Zhou, Y., Burd, C. E., & Zhang, J. (2016) · Leukemia · doi:10.1038/leu.2016.89 · Cited by 26
The spatiotemporal regulation of RAS signalling
Herrero, A., Matallanas, D., & Kölch, W. (2016) · Biochemical Society Transactions · doi:10.1042/bst20160127 · Cited by 26
Drosten, M., Simón-Carrasco, L., Hernández-Porras, I., Lechuga, C. G., Blasco, M. T., Jacob, H. K. C., Fabbiano, S., Potenza, N., Bustelo, X. R., Guerra, C. E., et al. (2016) · Cancer Research · doi:10.1158/0008-5472.can-16-2925 · Cited by 26
“RAS genes have also attracted interest due to their involvement in tumor development (1, 2).”
BackgroundSelf-citationBaines, A. T., Lim, K., Shields, J. M., Lambert, J. M., Counter, C. M., Der, C. J., & Cox, A. D. (2006) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(05)07045-x · Cited by 26
Mouse models of K-ras-initiated carcinogenesis
Janssen, K., Abala, M., Marjou, F. E., Louvard, D., & Robine, S. (2005) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2005.07.004 · Cited by 26
Lokhandwala, J., Smalley, T. B., & Tran, T. H. (2024) · Frontiers in Oncology · doi:10.3389/fonc.2024.1394702 · Cited by 28
miR-1297 promotes cell proliferation by inhibiting RB1 in liver cancer
Liu, C., Wang, C., Wang, J., & Huang, H. (2016) · Oncology Letters · doi:10.3892/ol.2016.5326 · Cited by 25
“However, in limited cases, the binding sites are located in the 5' UTR or in the coding region of the target mRNA (6). miRNAs are important in regulating various biological processes, including cell development, cell proliferation, cell differentiation and cell apoptosis.”
Runx3 plays a critical role in restriction-point and defense against cellular transformation
Chi, X.-Z., Lee, J., Lee, Y.-S., Park, I. Y., Ito, Y., & Bae, S.-C. (2017) · Oncogene · doi:10.1038/onc.2017.290 · Cited by 25
Metadata
- Authors
- Malumbres, M., & Barbacid, M.
- Affiliations
- Spanish National Cancer Research Centre (ES)
- Corresponding author
- Malumbres, Marcos
- Barbacid, Mariano
- Venue
- Nature Reviews Cancer
- Published
- 2003-06-01
- Volume
- 3
- Issue
- 6
- Pages
- 459-465
- ISSN
- 1474-175X (ISSN-L)
- 1474-1768
- OpenAlex
- W2083695927
- Cited by
- 1,902
- References
- 122
- Citations by year
- 2026: 39 · 2025: 77 · 2024: 94 · 2023: 84 · 2022: 89 · 2021: 78 · 2020: 68 · 2019: 74 · 2018: 80 · 2017: 99 · 2016: 91 · 2015: 98 · 2014: 117 · 2013: 120 · 2012: 104
- FWCI
- 3.49
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature reviews. Cancer (publishedVersion)
- PubMed (publishedVersion)
- 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 › Protein Tyrosine Phosphatases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Keywords
- oncogenic Ras, signal transduction, molecular oncology, RAS inhibitors, cancer therapy
- MeSH terms
- Animals, Humans, Genes, ras, Biomedical Research, History, 20th Century, History, 21st Century
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