Oncogenic Kras drives invasion and maintains metastases in colorectal cancer
Open accessAbstract
Human colorectal cancer (CRC) is a major cause of cancer mortality and frequently harbors activating mutations in the KRAS gene. To understand the role of oncogenic KRAS in CRC, we engineered a mouse model of metastatic CRC that harbors an inducible oncogenic Kras allele ( Kras mut ) and conditional null alleles of Apc and Trp53 (iKAP). The iKAP model recapitulates tumor progression from adenoma through metastases. Whole-exome sequencing revealed that the Kras mut allele was heterogenous in primary tumors yet homogenous in metastases, a pattern consistent with activated Kras mut signaling being a driver of progression to metastasis. System-level and functional analyses revealed the TGF-β pathway as a key mediator of Kras mut -driven invasiveness. Genetic extinction of Kras mut resulted in specific elimination of the Kras mut subpopulation in primary and metastatic tumors, leading to apoptotic elimination of advanced invasive and metastatic disease . This faithful CRC model provides genetic evidence that Kras mut drives CRC invasion and maintenance of metastases.
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
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?
Gene set enrichment analysis using cell-type-specific signatures discovered that the Paneth cell signature was the most significantly enriched epithelial cell type following combination treatment in iKAP tumors.
“We further conducted gene set enrichment analysis utilizing cell-type-specific signatures from a published RNA sequencing (RNA-seq) study32 and discovered that the Paneth cell signature was the most significantly enriched epithelial cell type following combination treatment (Figures 1E, 1F, and S1F).”
From Paneth-like transition drives resistance to dual targeting of KRAS and EGFR in colorectal cancer (2026) · cites this paper as [32]
The Results section reports RNA-seq profiling of iKAP tumors, so the source is a published RNA-seq study of the relevant model. But its reported enrichment analysis concerns invasive-tumor pathways and the CMS4 signature, not cell-type-specific or Paneth cell signatures. The Paneth enrichment following combination treatment is presented as the citing authors’ own finding, not a result attributed to this source. (LLM, conf=0.83)
Experimental — accuracy not yet measuredKRASG12D mutation is significantly associated with an increased risk of metastasis and a worse prognosis.
“and is significantly associated with an increased risk of metastasis and a worse prognosis [8].”
From Feedback activation of EGFR/wild-type RAS signaling axis limits KRASG12D inhibitor efficacy in KRASG12D-mutated colorectal cancer (2023) · cites this paper as [8]
The Results (Figure 1 and the accompanying text; page unavailable) identify the mouse-model mutation as KrasG12D and report metastases and significantly shorter tumor-free survival in mice carrying mutant Kras. This supports the claim in that model, but the paper does not establish that KRASG12D is significantly associated with worse prognosis in patients. (LLM, conf=0.86)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Siegel, R. L., Miller, K. D., & Jemal, A. (2016) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.21332 · Cited by 16,003 · see citing works
Smyth, G. K. (2004) · Statistical Applications in Genetics and Molecular Biology · doi:10.2202/1544-6115.1027 · Cited by 11,829 · see citing works
Oncogenic Kras maintains pancreatic tumors through regulation of anabolic glucose metabolism
Ying, H., Kimmelman, A. C., Lyssiotis, C. A., Hua, S., Chu, G. C., Fletcher-Sananikone, E., Locasale, J. W., Son, J., Zhang, H., Coloff, J. L., et al. (2012) · Cell · doi:10.1016/j.cell.2012.01.058 · Cited by 2,043 · see citing works
Self-citationThe molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers
Diaz Jr, L. A., Williams, R. T., Wu, J., Kinde, I., Hecht, J. R., Berlin, J., Allen, B., Bozic, I., Reiter, J. G., Nowak, M. A., et al. (2012) · Nature · doi:10.1038/nature11219 · Cited by 1,713 · see citing works
Yap1 Activation Enables Bypass of Oncogenic Kras Addiction in Pancreatic Cancer
Kapoor, A., Yao, W., Ying, H., Hua, S., Liewen, A., Wang, Q., Zhong, Y., Wu, C.-J., Sadanandam, A., Hu, B., et al. (2014) · Cell · doi:10.1016/j.cell.2014.06.003 · Cited by 716 · cited 1× · see citing works
“…of pathways downstream from activated KRAS (Pylayeva-Gupta et al. 2011), the existence of alternative KRAS-independent proliferation/ survival signaling pathways such as YAP (Kapoor et al. 2014), and/or the intratumoral genomic heterogeneity of the KRAS mut allele across the cancer cell population.”
Self-citationA targeted chain-termination mutation in the mouse Apc gene results in multiple intestinal tumors.
Fodde, R., Edelmann, W., Yang, K., van Leeuwen, C., Carlson, C., Renault, B., Breukel, C., Alt, E., Lipkin, M., & Khan, P. M. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.19.8969 · Cited by 531 · see citing works
Knijn, N., Mekenkamp, L. J. M., Klomp, M., Vink-Börger, M. E., Tol, J., Teerenstra, S., Meijer, J. W. R., Tebar, M., Riemersma, S., van Krieken, J. H. J. M., et al. (2011) · British Journal of Cancer · doi:10.1038/bjc.2011.26 · Cited by 291 · see citing works
A two-step model for colon adenoma initiation and progression caused by APC loss
Phelps, R. A., Chidester, S., Dehghanizadeh, S., Phelps, J., Sandoval, I. T., Rai, K., Broadbent, T., Sarkar, S., Burt, R. W., & Jones, D. A. (2009) · Cell · doi:10.1016/j.cell.2009.02.037 · Cited by 286 · see citing works
Association between KRAS mutation and lung metastasis in advanced colorectal cancer
Pereira, A. A. L., Rego, J. F. M., Morris, V, Overman, M. J., Eng, C., Garrett, C. R., Boutin, A. T., Ferrarotto, R., Lee, M., Jiang, Z.-Q., et al. (2015) · British Journal of Cancer · doi:10.1038/bjc.2014.619 · Cited by 94 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 49
- Anders S, Pyl PT, Huber W. 2015 HTSeq—a Python framework to work with high-throughput sequencing data. Bioinformatics 31: 166– 169. 25260700 PMC4287950
- Belteki G, Haigh J, Kabacs N, Haigh K, Sison K, Costantini F, Whitsett J, Quaggin SE, Nagy A. 2005 Conditional and inducible transgene expression in mice through the combinatorial use of Cre-mediated recombination and tetracycline induction. Nucleic Acids Res 33: e51. 15784609 PMC1069131
- Chanrion M, Kuperstein I, Barriere C, El Marjou F, Cohen D, Vignjevic D, Stimmer L, Paul-Gilloteaux P, Bieche I, Tavares SD, 2014 Concomitant Notch activation and p53 deletion trigger epithelial-to-mesenchymal transition and metastasis in mouse gut. Nat Commun 5: 5005. 25295490 PMC4214431
- Chin L, Tam A, Pomerantz J, Wong M, Holash J, Bardeesy N, Shen Q, O'Hagan R, Pantginis J, Zhou H, 1999 Essential role for oncogenic Ras in tumour maintenance. Nature 400: 468– 472. 10440378
- David CJ, Huang YH, Chen M, Su J, Zou Y, Bardeesy N, Iacobuzio-Donahue CA, Massague J. 2016 TGF-β tumor suppression through a lethal EMT. Cell 164: 1015– 1030. 26898331 PMC4801341
- de Hoon MJ, Imoto S, Nolan J, Miyano S. 2004 Open source clustering software. Bioinformatics 20: 1453– 1454. 14871861
- Dembele D, Kastner P. 2014 Fold change rank ordering statistics: a new method for detecting differentially expressed genes. BMC Bioinformatics 15: 14. 24423217 PMC3899927
- Dow LE, O'Rourke KP, Simon J, Tschaharganeh DF, van Es JH, Clevers H, Lowe SW. 2015 Apc restoration promotes cellular differentiation and reestablishes crypt homeostasis in colorectal cancer. Cell 161: 1539– 1552. 26091037 PMC4475279
- El Marjou F, Janssen KP, Chang BH, Li M, Hindie V, Chan L, Louvard D, Chambon P, Metzger D, Robine S. 2004 Tissue-specific and inducible Cre-mediated recombination in the gut epithelium. Genesis 39: 186– 193. 15282745
- Fearon ER, Vogelstein B. 1990 A genetic model for colorectal tumorigenesis. Cell 61: 759– 767. 2188735
- Fujimoto K, Sheng H, Shao J, Beauchamp RD. 2001 Transforming growth factor-β1 promotes invasiveness after cellular transformation with activated Ras in intestinal epithelial cells. Exp Cell Res 266: 239– 249. 11399052
- Gentleman RC, Carey VJ, Bates DM, Bolstad B, Dettling M, Dudoit S, Ellis B, Gautier L, Ge Y, Gentry J, 2004 Bioconductor: open software development for computational biology and bioinformatics. Genome Biol 5: R80. 15461798 PMC545600
- Guinney J, Dienstmann R, Wang X, de Reynies A, Schlicker A, Soneson C, Marisa L, Roepman P, Nyamundanda G, Angelino P, 2015 The consensus molecular subtypes of colorectal cancer. Nat Med 21: 1350– 1356. 26457759 PMC4636487
- Hinoi T, Akyol A, Theisen BK, Ferguson DO, Greenson JK, Williams BO, Cho KR, Fearon ER. 2007 Mouse model of colonic adenoma-carcinoma progression based on somatic Apc inactivation. Cancer Res 67: 9721– 9730. 17942902
- Humphries A, Wright NA. 2008 Colonic crypt organization and tumorigenesis. Nat Rev Cancer 8: 415– 424. 18480839
- Hung KE, Maricevich MA, Richard LG, Chen WY, Richardson MP, Kunin A, Bronson RT, Mahmood U, Kucherlapati R. 2010 Development of a mouse model for sporadic and metastatic colon tumors and its use in assessing drug treatment. Proc Natl Acad Sci 107: 1565– 1570. 20080688 PMC2824379
- Janssen KP, Alberici P, Fsihi H, Gaspar C, Breukel C, Franken P, Rosty C, Abal M, El Marjou F, Smits R, 2006 APC and oncogenic KRAS are synergistic in enhancing Wnt signaling in intestinal tumor formation and progression. Gastroenterology 131: 1096– 1109. 17030180
- Johnson RL, Fleet JC. 2013 Animal models of colorectal cancer. Cancer Metastasis Rev 32: 39– 61. 23076650 PMC3572245
- Jonkers J, Berns A. 2002 Conditional mouse models of sporadic cancer. Nat Rev Cancer 2: 251– 265. 12001987
- Kuraguchi M, Wang XP, Bronson RT, Rothenberg R, Ohene-Baah NY, Lund JJ, Kucherlapati M, Maas RL, Kucherlapati R. 2006 Adenomatous polyposis coli (APC) is required for normal development of skin and thymus. PLoS Genet 2: e146. 17002498 PMC1564426
- Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, Marth G, Abecasis G, Durbin R, Genome Project Data Processing Subgroup. 2009 The sequence alignment/map format and SAMtools. Bioinformatics 25: 2078– 2079. 19505943 PMC2723002
- Li HT, Lu YY, An YX, Wang X, Zhao QC. 2011 KRAS, BRAF and PIK3CA mutations in human colorectal cancer: relationship with metastatic colorectal cancer. Oncol Rep 25: 1691– 1697. 21424126
- Mannan A, Hahn-Stromberg V. 2012 K-ras mutations are correlated to lymph node metastasis and tumor stage, but not to the growth pattern of colon carcinoma. APMIS 120: 459– 468. 22583358
- Marino S, Vooijs M, van Der Gulden H, Jonkers J, Berns A. 2000 Induction of medulloblastomas in p53-null mutant mice by somatic inactivation of Rb in the external granular layer cells of the cerebellum. Genes Dev 14: 994– 1004. 10783170 PMC316543
- Marusyk A, Almendro V, Polyak K. 2012 Intra-tumour heterogeneity: a looking glass for cancer? Nat Rev Cancer 12: 323– 334. 22513401
- Misale S, Yaeger R, Hobor S, Scala E, Janakiraman M, Liska D, Valtorta E, Schiavo R, Buscarino M, Siravegna G, 2012 Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer. Nature 486: 532– 536. 22722830 PMC3927413
- Modest DP, Stintzing S, Laubender RP, Neumann J, Jung A, Giessen C, Haas M, Aubele P, Schulz C, Boeck S, 2011 Clinical characterization of patients with metastatic colorectal cancer depending on the KRAS status. Anticancer Drugs 22: 913– 918. 21795973
- Moser AR, Pitot HC, Dove WF. 1990 A dominant mutation that predisposes to multiple intestinal neoplasia in the mouse. Science 247: 322– 324. 2296722
- Muzumdar MD, Tasic B, Miyamichi K, Li L, Luo L. 2007 A global double-fluorescent Cre reporter mouse. Genesis 45: 593– 605. 17868096
- Novelli MR, Williamson JA, Tomlinson IP, Elia G, Hodgson SV, Talbot IC, Bodmer WF, Wright NA. 1996 Polyclonal origin of colonic adenomas in an XO/XY patient with FAP. Science 272: 1187– 1190. 8638166
- Oft M, Peli J, Rudaz C, Schwarz H, Beug H, Reichmann E. 1996 TGF-β1 and Ha-Ras collaborate in modulating the phenotypic plasticity and invasiveness of epithelial tumor cells. Genes Dev 10: 2462– 2477. 8843198
- Oshima M, Oshima H, Kitagawa K, Kobayashi M, Itakura C, Taketo M. 1995 Loss of Apc heterozygosity and abnormal tissue building in nascent intestinal polyps in mice carrying a truncated Apc gene. Proc Natl Acad Sci 92: 4482– 4486. 7753829 PMC41968
- Parsons BL. 2008 Many different tumor types have polyclonal tumor origin: evidence and implications. Mutat Res 659: 232– 247. 18614394
- Pollard P, Deheragoda M, Segditsas S, Lewis A, Rowan A, Howarth K, Willis L, Nye E, McCart A, Mandir N, 2009 The Apc 1322T mouse develops severe polyposis associated with submaximal nuclear β-catenin expression. Gastroenterology 136: 2204– 2213.e13. 19248780
- Preston SL, Wong WM, Chan AO, Poulsom R, Jeffery R, Goodlad RA, Mandir N, Elia G, Novelli M, Bodmer WF, 2003 Bottom-up histogenesis of colorectal adenomas: origin in the monocryptal adenoma and initial expansion by crypt fission. Cancer Res 63: 3819– 3825. 12839979
- Pylayeva-Gupta Y, Grabocka E, Bar-Sagi D. 2011 RAS oncogenes: weaving a tumorigenic web. Nat Rev Cancer 11: 761– 774. 21993244 PMC3632399
- Robanus-Maandag EC, Koelink PJ, Breukel C, Salvatori DC, Jagmohan-Changur SC, Bosch CA, Verspaget HW, Devilee P, Fodde R, Smits R. 2010 A new conditional Apc-mutant mouse model for colorectal cancer. Carcinogenesis 31: 946– 952. 20176656
- Sansom OJ, Meniel V, Wilkins JA, Cole AM, Oien KA, Marsh V, Jamieson TJ, Guerra C, Ashton GH, Barbacid M, 2006 Loss of Apc allows phenotypic manifestation of the transforming properties of an endogenous K-ras oncogene in vivo. Proc Natl Acad Sci 103: 14122– 14127. 16959882 PMC1599922
- Sasai H, Masaki M, Wakitani K. 2000 Suppression of polypogenesis in a new mouse strain with a truncated Apc(Delta474) by a novel COX-2 inhibitor, JTE-522. Carcinogenesis 21: 953– 958. 10783317
- Shibata H, Toyama K, Shioya H, Ito M, Hirota M, Hasegawa S, Matsumoto H, Takano H, Akiyama T, Toyoshima K, 1997 Rapid colorectal adenoma formation initiated by conditional targeting of the Apc gene. Science 278: 120– 123. 9311916
- Siegel PM, Massague J. 2003 Cytostatic and apoptotic actions of TGF-β in homeostasis and cancer. Nat Rev Cancer 3: 807– 821. 14557817
- Singh A, Sweeney MF, Yu M, Burger A, Greninger P, Benes C, Haber DA, Settleman J. 2012 TAK1 inhibition promotes apoptosis in KRAS-dependent colon cancers. Cell 148: 639– 650. 22341439 PMC3291475
- Sotillo R, Schvartzman JM, Socci ND, Benezra R. 2010 Mad2-induced chromosome instability leads to lung tumour relapse after oncogene withdrawal. Nature 464: 436– 440. 20173739 PMC2841716
- Su LK, Kinzler KW, Vogelstein B, Preisinger AC, Moser AR, Luongo C, Gould KA, Dove WF. 1992 Multiple intestinal neoplasia caused by a mutation in the murine homolog of the APC gene. Science 256: 668– 670. 1350108
- Taketo MM, Edelmann W. 2009 Mouse models of colon cancer. Gastroenterology 136: 780– 798. 19263594
- Thliveris AT, Halberg RB, Clipson L, Dove WF, Sullivan R, Washington MK, Stanhope S, Newton MA. 2005 Polyclonality of familial murine adenomas: analyses of mouse chimeras with low tumor multiplicity suggest short-range interactions. Proc Natl Acad Sci 102: 6960– 6965. 15870186 PMC1100801
- Wong MH, Saam JR, Stappenbeck TS, Rexer CH, Gordon JI. 2000 Genetic mosaic analysis based on Cre recombinase and navigated laser capture microdissection. Proc Natl Acad Sci 97: 12601– 12606. 11050178 PMC18810
- Wood LD, Parsons DW, Jones S, Lin J, Sjoblom T, Leary RJ, Shen D, Boca SM, Barber T, Ptak J, 2007 The genomic landscapes of human breast and colorectal cancers. Science 318: 1108– 1113. 17932254
- Xue Y, Johnson R, Desmet M, Snyder PW, Fleet JC. 2010 Generation of a transgenic mouse for colorectal cancer research with intestinal Cre expression limited to the large intestine. Mol Cancer Res 8: 1095– 1104. 20663863 PMC2923672
Cited by
Sorted by citations
KRAS-IRF2 axis drives immune suppression and immune therapy resistance in colorectal cancer
Liao, W., Overman, M. J., Boutin, A. T., Shang, X., Zhao, D., Dey, P., Li, J., Wang, G., Lan, Z., Li, J., et al. (2019) · Cancer Cell · doi:10.1016/j.ccell.2019.02.008 · Cited by 617 · see citing works
Self-citationWNT as a Driver and Dependency in Cancer
Parsons, M. J., Tammela, T., & Dow, L. E. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-21-0190 · Cited by 257 · see citing works
RAS: Striking at the Core of the Oncogenic Circuitry
Gimple, R. C., & Wang, X. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00965 · Cited by 174 · see citing works
Sakai, E., Nakayama, M., Oshima, H., Kouyama, Y., Niida, A., Fujii, S., Ochiai, A., Nakayama, K. I., Mimori, K., Suzuki, Y., et al. (2018) · Cancer Research · doi:10.1158/0008-5472.can-17-3303 · Cited by 133 · see citing works
Oncogenic KRAS Drives Lipofibrogenesis to Promote Angiogenesis and Colon Cancer Progression
Hsu, W.-H., LaBella, K. A., Lin, Y., Xu, P., Lee, R., Hsieh, C.-E., Yang, L., Zhou, A., Blecher, J. M., Wu, C.-J., et al. (2023) · Cancer Discovery · doi:10.1158/2159-8290.cd-22-1467 · Cited by 125 · see citing works
Self-citationFeng, J., Hu, Z., Xia, X., Liu, X., Lian, Z., Wang, H., Wang, L., Wang, C., Zhang, X., & Pang, X. (2023) · Oncogene · doi:10.1038/s41388-023-02676-9 · Cited by 95 · see citing works
“In particular, KRAS mutation is a more prevalent event, accounting for 10–12% of CRC cases [7] and is significantly associated with an increased risk of metastasis and a worse prognosis [8].”
BackgroundBrubaker, D. K., Paulo, J. A., Sheth, S., Poulin, E. J., Popow, O., Joughin, B. A., Strasser, S. D., Starchenko, A., Gygi, S. P., Lauffenburger, D. A., et al. (2019) · Cell Systems · doi:10.1016/j.cels.2019.07.006 · Cited by 57 · see citing works
“TGFB signaling was induced by KrasG12D in colonic tumors (Figure 4), and this pathway was previously shown to regulate metastasis in Kras mutant mouse colonic tumors (Boutin et al., 2017).”
BackgroundRecent Updates on the Significance of KRAS Mutations in Colorectal Cancer Biology
László, L., Kurilla, A., Takács, T., Kudlik, G., Koprivanacz, K., Buday, L., & Vas, V. (2021) · Cells · doi:10.3390/cells10030667 · Cited by 58 · see citing works
Gu, M., Gao, Y., & Chang, P. (2021) · Cancers · doi:10.3390/cancers13102429 · Cited by 35 · see citing works
Paneth-like transition drives resistance to dual targeting of KRAS and EGFR in colorectal cancer
Zhang, Y., Chen, J., She, Y., Fang, Z., Zhang, Y., Ruan, D., Guo, W., Liao, J., Zhou, W., Lao, J., et al. (2026) · Cancer Cell · doi:10.1016/j.ccell.2025.10.010 · Cited by 23 · see citing works
“32 Autochthonous CRC tumors were induced in iKAP mice via enema administration of 4-hydroxytamoxifen and doxycycline water at 8 weeks of age.”
Self-citationRathore, M., Zhang, W., Wright, M., Bhattacharya, R., Fan, F., Vaziri-Gohar, A., Winter, J., Wang, Z., Markowitz, S. D., Willis, J., et al. (2022) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-21-0633 · Cited by 14 · see citing works
Foote, J. B., Mattox, T. E., Keeton, A. B., Chen, X., Smith, F., Berry, K. L., Holmes, T., Wang, J., Huang, C.-H., Ward, A. B., et al. (2023) · doi:10.1101/2023.05.17.541233 · Cited by 13 · see citing works
- Authors
- Boutin, A. T., Liao, W.-T., Wang, M., Hwang, S. S., Karpinets, T. V., Cheung, H., Chu, G. C., Jiang, S., Hu, J., Chang, K., Vilar, E., Song, X., Zhang, J., Kopetz, S., Futreal, A., Wang, Y. A., Kwong, L. N., & DePinho, R. A.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- ORCID
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2017-02-15
- Volume
- 31
- Issue
- 4
- Pages
- 370-382
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC5358757
- OpenAlex
- W2597230258
- Cited by
- 195
- References
- 9
- Citations by year
- 2026: 14 · 2025: 25 · 2024: 25 · 2023: 28 · 2022: 20 · 2021: 30 · 2020: 17 · 2019: 18 · 2018: 15 · 2017: 3
- Type
- posted content
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Genes & Development (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- The Helen Hay Whitney Foundation
- University of Texas
- National Institutes of Health (R01 CA084628)
- Topics
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- oncogenic KRAS, colorectal cancer, metastasis, tumor invasion, TGF-beta signaling, APC, Trp53, conditional knockout mouse model, tumor heterogeneity, apoptosis, adenoma-carcinoma sequence
- MeSH terms
- Animals, Disease Models, Animal, Genotype, Humans, Mice, Inbred C57BL, Mutation, Neoplasm Invasiveness, Neoplasm Metastasis, Colorectal Neoplasms, Transforming Growth Factor beta, Proto-Oncogene Proteins p21(ras), Cell Line, Tumor, Mice, Transcriptome
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
