The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Stage-specific sensitivity to p53 restoration during lung cancer progression
Open accessAbstract
Tumorigenesis is a multistep process that results from the sequential accumulation of mutations in key oncogene and tumour suppressor pathways. Personalized cancer therapy that is based on targeting these underlying genetic abnormalities presupposes that sustained inactivation of tumour suppressors and activation of oncogenes is essential in advanced cancers. Mutations in the p53 tumour-suppressor pathway are common in human cancer and significant efforts towards pharmaceutical reactivation of defective p53 pathways are underway. Here we show that restoration of p53 in established murine lung tumours leads to significant but incomplete tumour cell loss specifically in malignant adenocarcinomas, but not in adenomas. We define amplification of MAPK signalling as a critical determinant of malignant progression and also a stimulator of Arf tumour-suppressor expression. The response to p53 restoration in this context is critically dependent on the expression of Arf. We propose that p53 not only limits malignant progression by suppressing the acquisition of alterations that lead to tumour progression, but also, in the context of p53 restoration, responds to increased oncogenic signalling to mediate tumour regression. Our observations also underscore that the p53 pathway is not engaged by low levels of oncogene activity that are sufficient for early stages of lung tumour development. These data suggest that restoration of pathways important in tumour progression, as opposed to initiation, may lead to incomplete tumour regression due to the stage-heterogeneity of tumour cell populations.
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Cites
Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a
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Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas
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Restoration of p53 function leads to tumour regression in vivo
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“Experimental restoration of p53 tumour-suppressor function has highlighted the potential for therapeutic intervention of this pathway to treat cancer and has uncovered a diversity of anti-tumour responses in different tumour types4–6.”
Self-citationTuveson, D. A., Shaw, A. T., Willis, N. A., Silver, D. P., Jackson, E. L., Chang, S., Mercer, K. L., Grochow, R., Hock, H., Crowley, D., et al. (2004) · Cancer Cell · doi:10.1016/s1535-6108(04)00085-6 · Cited by 798
Self-citationHaigis, K. M., Kendall, K. R., Wang, Y., Cheung, A., Haigis, M. C., Glickman, J. N., Niwa-Kawakita, M., Sweet-Cordero, A., Sebolt-Leopold, J., Shannon, K. M., et al. (2008) · Nature Genetics · doi:10.1038/ng.115 · Cited by 610
Self-citationModeling the Therapeutic Efficacy of p53 Restoration in Tumors
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Dose-dependent oncogene-induced senescence in vivo and its evasion during mammary tumorigenesis
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Reactivation of mutant p53: molecular mechanisms and therapeutic potential
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Cited by
Chien, Y., Scuoppo, C., Wang, X., Fang, X., Balgley, B., Bolden, J. E., Premsrirut, P., Luo, W., Chicas, A., Lee, C. S., et al. (2011) · Genes & Development · doi:10.1101/gad.17276711 · Cited by 1,046
Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy
Skoulidis, F., & Heymach, J. V. (2019) · Nature Reviews Cancer · doi:10.1038/s41568-019-0179-8 · Cited by 1,019
Antioxidants Accelerate Lung Cancer Progression in Mice
Sayin, V. I., Ibrahim, M. X., Larsson, E., Nilsson, J. A., Lindahl, P., & Bergo, M. O. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3007653 · Cited by 867
Senescence and aging: the critical roles of p53
Rufini, A., Tucci, P., Celardo, I., & Melino, G. (2013) · Oncogene · doi:10.1038/onc.2012.640 · Cited by 798
CRISPR-mediated direct mutation of cancer genes in the mouse liver
Xue, W., Chen, S., Yin, H., Tammela, T., Papagiannakopoulos, T., Joshi, N. S., Cai, W., Yang, G., Bronson, R., Crowley, D. G., et al. (2014) · Nature · doi:10.1038/nature13589 · Cited by 776
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Metadata
- Authors
- Feldser, D. M., Kostova, K. K., Winslow, M. M., Taylor, S. E., Cashman, C., Whittaker, C. A., Sanchez-Rivera, F. J., Resnick, R., Bronson, R., Hemann, M. T., & Jacks, T.
- Venue
- Nature
- Published
- 2010-11
- Volume
- 468
- Issue
- 7323
- Pages
- 572-575
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2160368760
- Cited by
- 273
- References
- 9
- FWCI
- 11.11
- Type
- journal article
- Language
- en
- Open access
- green
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- Feldser, D. M., Kostova, K. K., Winslow, M. M., Taylor, S. E., Cashman, C., Whittaker, C. A., Sanchez-Rivera, F. J., Resnick, R., Bronson, R., Hemann, M. T., & Jacks, T. (2010). Stage-specific sensitivity to p53 restoration during lung cancer progression. Nature. https://doi.org/10.1038/nature09535
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