The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
SIRT6 Suppresses Pancreatic Cancer through Control of Lin28b
Open accessAbstract
Chromatin remodeling proteins are frequently dysregulated in human cancer, yet little is known about how they control tumorigenesis. Here, we uncover an epigenetic program mediated by the NAD+-dependent histone deacetylase Sirtuin 6 (SIRT6) that is critical for suppression of pancreatic ductal adenocarcinoma (PDAC), one of the most lethal malignancies. SIRT6 inactivation accelerates PDAC progression and metastasis via upregulation of Lin28b, a negative regulator of the let-7 microRNA. SIRT6 loss results in histone hyperacetylation at the Lin28b promoter, Myc recruitment, and pronounced induction of Lin28b and downstream let-7 target genes, HMGA2, IGF2BP1 and IGF2BP3. This epigenetic program defines a distinct subset with a poor prognosis, representing 30–40% of human PDAC, characterized by reduced SIRT6 expression and an exquisite dependence on Lin28b for tumor growth. Thus, we identify SIRT6 as an important PDAC tumor suppressor, and uncover the Lin28b pathway as a potential therapeutic target in a molecularly-defined PDAC subset.
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Citations
Cites
The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity
Barretina, J., Caponigro, G., Stransky, N., Venkatesan, K., Margolin, A. A., Kim, S., Wilson, C. J., Lehár, J., Kryukov, G. V., Sonkin, D., et al. (2012) · Nature · doi:10.1038/nature11003 · Cited by 7,950
RAS Is Regulated by the let-7 MicroRNA Family
Johnson, S. M., Grosshans, H., Shingara, J., Byrom, M., Jarvis, R., Cheng, A., Labourier, E., Reinert, K. L., Brown, D., & Slack, F. J. (2005) · Cell · doi:10.1016/j.cell.2005.01.014 · Cited by 3,656
Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA
Pasquinelli, A. E., Reinhart, B. J., Slack, F., Martindale, M. Q., Kuroda, M. I., Maller, B., Hayward, D. C., Ball, E. E., Degnan, B., Müller, P., et al. (2000) · Nature · doi:10.1038/35040556 · Cited by 2,565
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Self-citationPancreatic cancer genomes reveal aberrations in axon guidance pathway genes
Initiative, A. P. C. G., Biankin, A. V., Waddell, N., Kassahn, K. S., Gingras, M.-C., Muthuswamy, L. B., Johns, A. L., Miller, D. K., Wilson, P. J., Patch, A.-M., et al. (2012) · Nature · doi:10.1038/nature11547 · Cited by 2,058 · cited 1×
“Moreover, gene set enrichment analysis (GSEA) comparing PDAC tumors (Badea et al., 2008; Biankin et al., 2012; Pei et al., 2009; Pérez-Mancera et al., 2012; Zhang et al., 2012) and cell lines (Barretina et al., 2012) (Table S3) with high versus low expression of LIN28B revealed that LIN28Bhigh…”
MethodOncogenic Kras maintains pancreatic tumors through regulation of anabolic glucose metabolism
Ying, H., Kimmelman, A. C., Lyssiotis, C. A., Hua, S., Chu, G. C., Fletcher-Sananikone, E., Locasale, J. W., Son, J., Zhang, H., Coloff, J. L., et al. (2012) · Cell · doi:10.1016/j.cell.2012.01.058 · Cited by 2,043
Analysis of lung tumor initiation and progression using conditional expression of oncogenic K-ras
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Genomic Instability and Aging-like Phenotype in the Absence of Mammalian SIRT6
Mostoslavsky, R., Chua, K. F., Lombard, D. B., Pang, W. W., Fischer, M. R., Gellon, L., Liu, P., Mostoslavsky, G., Franco, S., Murphy, M. M., et al. (2006) · Cell · doi:10.1016/j.cell.2005.11.044 · Cited by 1,637
Self-citationSelective Blockade of MicroRNA Processing by Lin28
Viswanathan, S. R., Daley, G. Q., & Gregory, R. I. (2008) · Science · doi:10.1126/science.1154040 · Cited by 1,437
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Cited by
Slowing ageing by design: the rise of NAD+ and sirtuin-activating compounds
Bonkowski, M. S., & Sinclair, D. A. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.93 · Cited by 834
Interplay between Metabolism and Epigenetics: A Nuclear Adaptation to Environmental Changes
Etchegaray, J.-P., & Mostoslavsky, R. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.05.029 · Cited by 518
Self-citationSirtuin activators and inhibitors: Promises, achievements, and challenges
Dai, H., Sinclair, D. A., Ellis, J. L., & Steegborn, C. (2018) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2018.03.004 · Cited by 463
“These findings indicate that molecules that activate sirtuins in humans may not only provide broad health benefits with potent anti-inflammatory, cardio-protective, neuroprotective, and anti-tumor activities (Kugel et al., 2016).”
BackgroundWang, S., Zheng, Y., Yang, F., Zhu, L., Zhu, X.-Q., Wang, Z.-F., Wu, X.-L., Zhou, C.-H., Yan, J.-Y., Hu, B.-Y., et al. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00659-4 · Cited by 369
SIRT6: Novel Mechanisms and Links to Aging and Disease
Tasselli, L., Zheng, W., & Chua, K. F. (2017) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2016.10.002 · Cited by 265
Metadata
- Authors
- Kugel, S., Sebastián, C., Fitamant, J., Ross, K. N., Saha, S. K., Jain, E., Gladden, A., Arora, K. S., Kato, Y., Rivera, M. N., Ramaswamy, S., Sadreyev, R. I., Goren, A., Deshpande, V., Bardeesy, N., & Mostoslavsky, R.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2016-06
- Volume
- 165
- Issue
- 6
- Pages
- 1401-1415
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2374078013
- Cited by
- 294
- References
- 49
- FWCI
- 17.14
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Kugel, S., Sebastián, C., Fitamant, J., Ross, K. N., Saha, S. K., Jain, E., Gladden, A., Arora, K. S., Kato, Y., Rivera, M. N., Ramaswamy, S., Sadreyev, R. I., Goren, A., Deshpande, V., Bardeesy, N., & Mostoslavsky, R. (2016). SIRT6 Suppresses Pancreatic Cancer through Control of Lin28b. Cell. https://doi.org/10.1016/j.cell.2016.04.033
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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.
