The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
Developmental Regulation of Mitochondrial Apoptosis by c-Myc Governs Age- and Tissue-Specific Sensitivity to Cancer Therapeutics
Open accessAbstract
SUMMARY It is not understood why healthy tissues can exhibit varying levels of sensitivity to the same toxic stimuli. Using BH3 Profiling, we find that mitochondria of many adult somatic tissues, including brain, heart and kidneys, are profoundly refractory to pro-apoptotic signaling, leading to cellular resistance to cytotoxic chemotherapies and ionizing radiation. In contrast, mitochondria from these tissues in young mice and humans are primed for apoptosis, predisposing them to undergo cell death in response to genotoxic damage. While expression of the apoptotic protein machinery is nearly absent by adulthood, in young tissues its expression is driven by c-Myc, linking developmental growth to cell death. These differences may explain why pediatric cancer patients have a higher risk of developing treatment-associated toxicities.
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Cited by
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Self-citationHow does p53 induce apoptosis and how does this relate to p53-mediated tumour suppression
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Necroptosis and RIPK1-mediated neuroinflammation in CNS diseases
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Fundamental Mechanisms of Regulated Cell Death and Implications for Heart Disease
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Metadata
- Authors
- Sarosiek, K. A., Fraser, C., Muthalagu, N., Bhola, P. D., Chang, W., McBrayer, S. K., Cantlon, A., Fisch, S., Golomb-Mello, G., Ryan, J. A., Deng, J., Jian, B., Corbett, C., Goldenberg, M., Madsen, J. R., Liao, R., Walsh, D., Sedivy, J., Murphy, D. J., Carrasco, D. R., Robinson, S., Moslehi, J., & Letai, A.
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2017-01
- Volume
- 31
- Issue
- 1
- Pages
- 142-156
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W2566496356
- Cited by
- 226
- References
- 8
- FWCI
- 11.59
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Sarosiek, K. A., Fraser, C., Muthalagu, N., Bhola, P. D., Chang, W., McBrayer, S. K., Cantlon, A., Fisch, S., Golomb-Mello, G., Ryan, J. A., Deng, J., Jian, B., Corbett, C., Goldenberg, M., Madsen, J. R., Liao, R., Walsh, D., Sedivy, J., Murphy, D. J., . . . Letai, A. (2017). Developmental Regulation of Mitochondrial Apoptosis by c-Myc Governs Age- and Tissue-Specific Sensitivity to Cancer Therapeutics. Cancer Cell. https://doi.org/10.1016/j.ccell.2016.11.011
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