The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Autophagy Inhibition Mediates Apoptosis Sensitization in Cancer Therapy by Relieving FOXO3a Turnover
Open accessAbstract
Summary Macroautophagy (autophagy) is intimately linked with cell death and allows cells to evade apoptosis. This has prompted clinical trials to combine autophagy inhibitors with other drugs with the aim of increasing the likelihood of cancer cells dying. However, the molecular basis for such effects is unknown. Here, we describe a transcriptional mechanism that connects autophagy to apoptosis. The autophagy-regulating transcription factor, FOXO3a, is itself turned over by basal autophagy creating a potential feedback loop. Increased FOXO3a upon autophagy inhibition stimulates transcription of the pro-apoptotic BBC3/PUMA gene to cause apoptosis sensitization. This mechanism explains how autophagy inhibition can sensitize tumor cells to chemotherapy drugs and allows an autophagy inhibitor to change the action of an MDM2-targeted drug from growth inhibition to apoptosis, reducing tumor burden in vivo. Thus, a link between two processes mediated via a single transcription factor binding site in the genome can be leveraged to improve anti-cancer therapies.
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Cites
Levy, J. M. M., Towers, C. G., & Thorburn, A. (2017) · Nature Reviews Cancer · doi:10.1038/nrc.2017.53 · Cited by 2,526
Self-citationSystematic identification of genomic markers of drug sensitivity in cancer cells
Garnett, M. J., Edelman, E. J., Heidorn, S. J., Greenman, C. D., Dastur, A., Lau, K. W., Greninger, P., Thompson, I. R., Luo, X., Soares, J., et al. (2012) · Nature · doi:10.1038/nature11005 · Cited by 2,456
Kimura, S., Noda, T., & Yoshimori, T. (2007) · Autophagy · doi:10.4161/auto.4451 · Cited by 2,278
Small-molecule MDM2 antagonists reveal aberrant p53 signaling in cancer: implications for therapy
Tovar, C., Rosinski, J., Filipovic, Z., Higgins, B., Kolinsky, K., Hilton, H., Zhao, X., Vu, B. T., Qing, W., Packman, K., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0507493103 · Cited by 708
Autophagy mediates degradation of nuclear lamina
Dou, Z., Xu, C., Donahue, G., Shimi, T., Pan, J.-A., Zhu, J., Ivanov, A., Capell, B. C., Drake, A. M., Shah, P. P., et al. (2015) · Nature · doi:10.1038/nature15548 · Cited by 655
FOXO3A directs a protective autophagy program in haematopoietic stem cells
Warr, M. R., Binnewies, M., Flach, J., Reynaud, D., Garg, T., Malhotra, R., Debnath, J., & Passegué, E. (2013) · Nature · doi:10.1038/nature11895 · Cited by 625
Gump, J. M., Staskiewicz, L., Morgan, M. J., Bamberg, A., Riches, D. W. H., & Thorburn, A. (2014) · Nature Cell Biology · doi:10.1038/ncb2886 · Cited by 230
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Cited by
Autophagy, cancer stem cells and drug resistance
Smith, A. G., & Macleod, K. F. (2019) · The Journal of Pathology · doi:10.1002/path.5222 · Cited by 365
The interplay of autophagy and non-apoptotic cell death pathways
(2020) · International Review of Cell and Molecular Biology · doi:10.1016/bs.ircmb.2019.12.004 · Cited by 50
Zhang, H., Steed, A., Co, M., & Chen, X. (2021) · Cancer Drug Resistance · doi:10.20517/cdr.2021.32 · Cited by 50
Autophagy: A Versatile Player in the Progression of Colorectal Cancer and Drug Resistance
Manzoor, S., Muhammad, J. S., Maghazachi, A. A., & Hamid, Q. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.924290 · Cited by 45
Metadata
- Authors
- Fitzwalter, B. E., Towers, C. G., Sullivan, K. D., Andrysik, Z., Hoh, M., Ludwig, M., O'Prey, J., Ryan, K. M., Espinosa, J. M., Morgan, M. J., & Thorburn, A.
- Venue
- Developmental Cell
- Publisher
- Elsevier BV
- Published
- 2018-03
- Volume
- 44
- Issue
- 5
- Pages
- 555-565.e3
- ISSN
- 1534-5807 (ISSN-L)
- OpenAlex
- W2792784918
- Cited by
- 206
- References
- 7
- FWCI
- 20.11
- Type
- journal article
- Language
- en
- Open access
- bronze
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- The paper
- Fitzwalter, B. E., Towers, C. G., Sullivan, K. D., Andrysik, Z., Hoh, M., Ludwig, M., O'Prey, J., Ryan, K. M., Espinosa, J. M., Morgan, M. J., & Thorburn, A. (2018). Autophagy Inhibition Mediates Apoptosis Sensitization in Cancer Therapy by Relieving FOXO3a Turnover. Developmental Cell. https://doi.org/10.1016/j.devcel.2018.02.014
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
