The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
Sprouty-2 regulates oncogenic K-ras in lung development and tumorigenesis
Open accessAbstract
Somatic activation of Ras occurs frequently in human cancers, including one-third of lung cancers. Activating Ras mutations also occur in the germline, leading to complex developmental syndromes. The precise mechanism by which Ras activation results in human disease is uncertain. Here we describe the phenotype of a mouse engineered to harbor a germline oncogenic K-ras G12D mutation. This mouse exhibits early embryonic lethality due to a placental trophoblast defect. Reconstitution with a wild-type placenta rescues the early lethality, but mutant embryos still succumb to cardiovascular and hematopoietic defects. In addition, mutant embryos demonstrate a profound defect in lung branching morphogenesis associated with striking up-regulation of the Ras/mitogen-activated protein kinase (MAPK) antagonist Sprouty-2 and abnormal localization of MAPK activity within the lung epithelium. This defect can be significantly suppressed by lentiviral short hairpin RNA (shRNA)-mediated knockdown of Sprouty-2 in vivo. Furthermore, in the context of K-ras G12D -mediated lung tumorigenesis, Sprouty-2 is also up-regulated and functions as a tumor suppressor to limit tumor number and overall tumor burden. These findings indicate that in the lung, Sprouty-2 plays a critical role in the regulation of oncogenic K-ras, and implicate counter-regulatory mechanisms in the pathogenesis of Ras-based disease.
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“Oncogenic Ras activation has been shown to increase the expression of Spry2, providing feedback inhibition of Ras activation (Shaw et al., 2007).”
From Modulation of K-Ras-Dependent Lung Tumorigenesis by MicroRNA-21 (2010) · cites this paper as Shaw et al., 2007
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“SPRY2, in turn, negatively regulates Ras/MEK/ERK signaling and is a tumor suppressor in NSCLC in both mice (Minowada and Miller, 2004; Minowada and Miller, 2009; Shaw et al., 2007) and humans (Sutterluty et al., 2007).”
From Modulation of K-Ras-Dependent Lung Tumorigenesis by MicroRNA-21 (2010) · cites this paper as Shaw et al., 2007
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Cites
Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a
Serrano, M., Lin, A. W., McCurrach, M. E., Beach, D., & Lowe, S. W. (1997) · Cell · doi:10.1016/s0092-8674(00)81902-9 · Cited by 5,218 · cited 1×
“However, recent data also point to an alternative mechanism of tumor suppression, namely, induction of oncogene-induced senescence (Serrano et al. 1997; Lin et al. 1998).”
Backgroundras oncogenes in human cancer: a review.
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Targeting RAS signalling pathways in cancer therapy
Downward, J. (2003) · Nature reviews. Cancer · doi:10.1038/nrc969 · Cited by 3,354
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Analysis of lung tumor initiation and progression using conditional expression of oncogenic K-rasPreprint
Jackson, E. L., Willis, N. A., Mercer, K. L., Bronson, R. T., Crowley, D. G., Montoya, R., Jacks, T., & Tuveson, D. A. (2001) · Genes & Development · doi:10.1101/gad.943001 · Cited by 1,927
Self-citationRAS oncogenes: the first 30 years
Malumbres, M., & Barbacid, M. (2003) · Nature Reviews Cancer · doi:10.1038/nrc1097 · Cited by 1,902 · cited 2×
“In addition to the canonical Ras effectors—Raf, PI3K, and RalGDS—at least seven other distinct Ras effector pathways have Shaw et al. 702 GENES & DEVELOPMENT been defined (Malumbres and Barbacid 2003).”
BackgroundRubinson, D. A., Dillon, C. P., Kwiatkowski, A. V., Sievers, C., Yang, L., Kopinja, J. E., Rooney, D. L., Zhang, M., Ihrig, M. M., McManus, M. T., et al. (2003) · Nature Genetics · doi:10.1038/ng1117 · Cited by 1,499
Somatic activation of the K-ras oncogene causes early onset lung cancer in mice
Johnson, L., Mercer, K., Greenbaum, D., Bronson, R. T., Crowley, D., Tuveson, D. A., & Jacks, T. (2001) · Nature · doi:10.1038/35074129 · Cited by 1,179
Self-citationFibroblast Growth Factor 10 (FGF10) and branching morphogenesis in the embryonic mouse lung
Bellusci, S., Grindley, J. C., Emoto, H., Itoh, N., & Hogan, B. L. M. (1997) · Development · doi:10.1242/dev.124.23.4867 · Cited by 1,006
Lin, A. W., Barradas, M., Stone, J. C., van Aelst, L., Serrano, M., & Lowe, S. W. (1998) · Genes & Development · doi:10.1101/gad.12.19.3008 · Cited by 945
Self-citation
Research works printed but not linked: 1
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Cited by
Sorted by citations
Modulation of K-Ras-Dependent Lung Tumorigenesis by MicroRNA-21
Hatley, M. E., Patrick, D. M., Garcia, M. R., Richardson, J. A., Bassel-Duby, R., van Rooij, E., & Olson, E. N. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.08.013 · Cited by 626
“SPRY2, in turn, negatively regulates Ras/MEK/ERK signaling and is a tumor suppressor in NSCLC in both mice (Minowada and Miller, 2004;Minowada andMiller, 2009; Shaw et al., 2007) and humans (Sutterluty et al., 2007).”
InfluentialPRC2 loss amplifies Ras-driven transcription and confers sensitivity to BRD4-based therapies
Raedt, T. D., Beert, E., Pasmant, É., Luscan, A., Brems, H., Ortonne, N., Helin, K., Hornick, J. L., Mautner, V., Kehrer‐Sawatzki, H., et al. (2014) · Nature · doi:10.1038/nature13561 · Cited by 473
Many roads lead to oncogene-induced senescence
Courtois-Cox, S., Jones, S. L., & Cichowski, K. (2008) · Oncogene · doi:10.1038/sj.onc.1210950 · Cited by 397
Programmed synthesis of three-dimensional tissues
Todhunter, M. E., Jee, N. Y., Hughes, A. J., Coyle, M. C., Cerchiari, A. E., Farlow, J., Garbe, J. C., LaBarge, M. A., Desai, T. A., & Gartner, Z. J. (2015) · Nature Methods · doi:10.1038/nmeth.3553 · Cited by 246
Selective activation of p53-mediated tumour suppression in high-grade tumours
Junttila, M. R., Karnezis, A. N., Garcia, D. A., Madriles, F., Kortlever, R. M., Rostker, F., Swigart, L. B., Pham, D. M., Seo, Y., Evan, G. I., et al. (2010) · Nature · doi:10.1038/nature09526 · Cited by 247
Metadata
- Authors
- Shaw, A. T., Meissner, A., Dowdle, J. A., Crowley, D., Magendantz, M., Ouyang, C., Parisi, T., Rajagopal, J., Blank, L. J., Bronson, R. T., Stone, J. R., Tuveson, D. A., Jaenisch, R., & Jacks, T.
- Affiliations
- Harvard University (US)
- Whitehead Institute for Biomedical Research (US)
- Massachusetts Institute of Technology (US)
- Howard Hughes Medical Institute (US)
- Tufts University (US)
- Corresponding author
- Jacks, Tyler
- ORCID
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2007-03-15
- Volume
- 21
- Issue
- 6
- Pages
- 694-707
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC1820943
- OpenAlex
- W2102049157
- Cited by
- 131
- References
- 49
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 2 · 2023: 5 · 2022: 3 · 2021: 4 · 2020: 2 · 2019: 5 · 2018: 3 · 2017: 3 · 2016: 9 · 2015: 11 · 2014: 6 · 2013: 9 · 2012: 7
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
- Funders
- Howard Hughes Medical Institute (P30-CA14051)
- Damon Runyon Cancer Research Foundation
- National Cancer Institute (5K08CA111634-2, 5-U01-CA84306-06, CA14051, U01CA084306, K08CA111634, P30CA014051, P30-CA-14051)
- 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 › Developmental Biology and Gene Regulation
- Keywords
- Sprouty2, KRAS G12D, lung development, lung carcinogenesis, lung branching morphogenesis, MAPK signaling, tumor suppressor, embryonic lethality, cardiovascular defects, hematopoietic defects
- MeSH terms
- Animals, Base Sequence, Female, Humans, Lung, Lung Neoplasms, Membrane Proteins, Mice, Transgenic, Pregnancy, Genes, ras, RNA, Gene Expression Regulation, Neoplastic, Protein Serine-Threonine Kinases, Germ-Line Mutation, Mice, Knockout, Gene Expression Regulation, Developmental, MAP Kinase Signaling System, Embryo Loss, Intracellular Signaling Peptides and Proteins, Adaptor Proteins, Signal Transducing, Mice
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