The DOI matches its Crossref record; 18 of the 18 references it cites were found in a registry or an index.
Tumorigenesis in tuberous sclerosis complex is autophagy and p62/sequestosome 1 (SQSTM1)-dependent
Open accessAbstract
Tuberous sclerosis complex (TSC) is a tumor suppressor syndrome characterized by benign tumors in multiple organs, including the brain and kidney. TSC-associated tumors exhibit hyperactivation of mammalian target of rapamycin complex 1 (mTORC1), a direct inhibitor of autophagy. Autophagy can either promote or inhibit tumorigenesis, depending on the cellular context. The role of autophagy in the pathogenesis and treatment of the multisystem manifestations of TSC is unknown. We found that the combination of mTORC1 and autophagy inhibition was more effective than either treatment alone in inhibiting the survival of tuberin (TSC2)-null cells, growth of TSC2-null xenograft tumors, and development of spontaneous renal tumors in Tsc2 +/− mice. Down-regulation of Atg5 induced extensive central necrosis in TSC2-null xenograft tumors, and loss of one allele of Beclin1 almost completely blocked macroscopic renal tumor formation in Tsc2 +/− mice. Surprisingly, given the finding that lowering autophagy blocks TSC tumorigenesis, genetic down-regulation of p62/sequestosome 1 (SQSTM1), the autophagy substrate that accumulates in TSC tumors as a consequence of low autophagy levels, strongly inhibited the growth of TSC2-null xenograft tumors. These data demonstrate that autophagy is a critical component of TSC tumorigenesis, suggest that mTORC1 inhibitors may have autophagy-dependent prosurvival effects in TSC, and reveal two distinct therapeutic targets for TSC: autophagy and the autophagy target p62/SQSTM1.
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Cites
Autophagy in the Pathogenesis of Disease
Levine, B., & Kroemer, G. (2008) · Cell · doi:10.1016/j.cell.2007.12.018 · Cited by 7,069
LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing.
Kabeya, Y., Mizushima, N., Ueno, T., Yamamoto, A., Kirisako, T., Noda, T., Kominami, E., Ohsumi, Y., & Yoshimori, T. (2000) · The EMBO Journal · doi:10.1093/emboj/19.21.5720 · Cited by 6,605
Autophagy fights disease through cellular self-digestion
Mizushima, N., Levine, B., Cuervo, A. M., & Klionsky, D. J. (2008) · Nature · doi:10.1038/nature06639 · Cited by 6,452
AKT/PKB signaling: navigating downstream
Manning, B. D., & Cantley, L. C. (2007) · Cell · doi:10.1016/j.cell.2007.06.009 · Cited by 6,115
TSC2 Mediates Cellular Energy Response to Control Cell Growth and Survival
Inoki, K., Zhu, T., & Guan, K.-L. (2003) · Cell · doi:10.1016/s0092-8674(03)00929-2 · Cited by 3,914
Bjørkøy, G., Lamark, T., Brech, A., Outzen, H., Perander, M., Øvervatn, A., Stenmark, H., & Johansen, T. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200507002 · Cited by 3,276
The role of autophagy during the early neonatal starvation period
Kuma, A., Hatano, M., Matsui, M., Yamamoto, A., Nakaya, H., Yoshimori, T., Ohsumi, Y., Tokuhisa, T., & Mizushima, N. (2004) · Nature · doi:10.1038/nature03029 · Cited by 2,865
Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene
Qu, X., Yu, J., Bhagat, G., Furuya, N., Hibshoosh, H., Troxel, A., Rosen, J., Eskelinen, E.-L., Mizushima, N., Ohsumi, Y., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci20039 · Cited by 2,311
Self-citationYue, Z., Jin, S., Yang, C., Levine, A. J., & Heintz, N. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2436255100 · Cited by 2,116
Nutrient-dependent mTORC1 Association with the ULK1–Atg13–FIP200 Complex Required for Autophagy
Hosokawa, N., Hara, T., Kaizuka, T., Kishi, C., Takamura, A., Miura, Y., Iemura, S.-I., Natsume, T., Takehana, K., Yamada, N., et al. (2009) · Molecular Biology of the Cell · doi:10.1091/mbc.e08-12-1248 · Cited by 2,076
Cited by
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Kim, Y. C., & Guan, K.-L. (2015) · Journal of Clinical Investigation · doi:10.1172/jci73939 · Cited by 2,126
Autophagy and autophagy-related proteins in cancer
Li, X., He, S., & Ma, B. (2020) · Molecular Cancer · doi:10.1186/s12943-020-1138-4 · Cited by 1,613
Autophagy modulation as a potential therapeutic target for diverse diseases
Rubinsztein, D. C., Codogno, P., & Levine, B. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3802 · Cited by 1,437
Autophagy in malignant transformation and cancer progression
Galluzzi, L., Pietrocola, F., Bravo‐San Pedro, J. M., Amaravadi, R. K., Baehrecke, E. H., Cecconi, F., Codogno, P., Debnath, J., Gewirtz, D. A., Karantza, V., et al. (2015) · The EMBO Journal · doi:10.15252/embj.201490784 · Cited by 1,182
TBC1D7 Is a Third Subunit of the TSC1-TSC2 Complex Upstream of mTORC1
Dibble, C. C., Elis, W., Menon, S., Qin, W., Klekota, J., Asara, J. M., Finan, P. M., Kwiatkowski, D. J., Murphy, L. O., & Manning, B. D. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.06.009 · Cited by 612
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Metadata
- Authors
- Parkhitko, A., Myachina, F., Morrison, T. A., Hindi, K. M., Auricchio, N., Karbowniczek, M., Wu, J. J., Finkel, T., Kwiatkowski, D. J., Yu, J. J., & Henske, E. P.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2011-07-11
- Volume
- 108
- Issue
- 30
- Pages
- 12455-12460
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2117849574
- Cited by
- 189
- References
- 18
- FWCI
- 14.83
- Type
- journal article
- Language
- en
- Open access
- green
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- Parkhitko, A., Myachina, F., Morrison, T. A., Hindi, K. M., Auricchio, N., Karbowniczek, M., Wu, J. J., Finkel, T., Kwiatkowski, D. J., Yu, J. J., & Henske, E. P. (2011). Tumorigenesis in tuberous sclerosis complex is autophagy and p62/sequestosome 1 (SQSTM1)-dependent. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1104361108
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