Abstract
Sirtuin 6 (SIRT6) is a member of the mammalian sirtuin family with deacetylase, deacylase, and mono-ADP-ribosyl-transferase activities. It is a multitasking chromatin-associated protein regulating different cellular and physiological functions in cells. Specifically, SIRT6 dysfunction is implicated in several aging-related human diseases, including cancer. Studies indicate that SIRT6 has a tumor-specific role, and it is considered a tumor suppressor as well as a tumor growth inducer, depending on the type of cancer. In this chapter, we review the role of SIRT6 in metabolism, genomic stability, and cancer. Further, we provide an insight into the interplay of the tumor-suppressing and oncogenic roles of SIRT6 in cancer. Additionally, we discuss the use of small-molecule SIRT6 modulators as potential therapeutics.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Albani D, Polito L, Forloni G (2010) Sirtuins as novel targets for Alzheimer’s disease and other neurodegenerative disorders: experimental and genetic evidence. J Alzheimers Dis 19(1):11–26. https://doi.org/10.3233/JAD-2010-1215
Antonia C, Debora S, Stefania O, Giovanna T, Paola M, Fabio G, Veronica R, Nicoletta C, Enrico C, Marino C, Maurizio M, Micaela B, Aimable N, Michel D, Katia T, Antonino N, Mario P, Santina B, Alessio N, Francesco B, Marco G, Roberto ML, Michele C (2018) Depletion of SIRT6 enzymatic activity increases acute myeloid leukemia cells’ vulnerability to DNA-damaging agents. Haematologica 103(1):80–90. https://doi.org/10.3324/haematol.2017.176248
Ardestani PM, Liang F (2012) Sub-cellular localization, expression and functions of Sirt6 during the cell cycle in HeLa cells. Nucleus 3(5):442–451. https://doi.org/10.4161/nucl.21134
Ashraf N, Zino S, Macintyre A, Kingsmore D, Payne AP, George WD, Shiels PG (2006) Altered sirtuin expression is associated with node-positive breast cancer. Br J Cancer 95(8):1056–1061. https://doi.org/10.1038/sj.bjc.6603384
Bai L, Lin G, Sun L, Liu Y, Huang X, Cao C, Guo Y, **e C (2016) Upregulation of SIRT6 predicts poor prognosis and promotes metastasis of non-small cell lung cancer via the ERK1/2/MMP9 pathway. Oncotarget 7(26):40377–40386. https://doi.org/10.18632/oncotarget.9750
Barber MF, Michishita-Kioi E, ** Y, Tasselli L, Kioi M, Moqtaderi Z, Tennen RI, Paredes S, Young NL, Chen K, Struhl K, Garcia BA, Gozani O, Li W, Chua KF (2012) SIRT7 links H3K18 deacetylation to maintenance of oncogenic transformation. Nature 487(7405):114–118. https://doi.org/10.1038/nature11043
Bhardwaj A, Das S (2016) SIRT6 deacetylates PKM2 to suppress its nuclear localization and oncogenic functions. Proc Natl Acad Sci U S A 113(5):E538–E547. https://doi.org/10.1073/pnas.1520045113
Bosch-Presegue L, Vaquero A (2011) The dual role of sirtuins in cancer. Genes Cancer 2(6):648–662. https://doi.org/10.1177/1947601911417862
Bradbury CA, Khanim FL, Hayden R, Bunce CM, White DA, Drayson MT, Craddock C, Turner BM (2005) Histone deacetylases in acute myeloid leukaemia show a distinctive pattern of expression that changes selectively in response to deacetylase inhibitors. Leukemia 19(10):1751–1759. https://doi.org/10.1038/sj.leu.2403910
Cai J, Zuo Y, Wang T, Cao Y, Cai R, Chen FL, Cheng J, Mu J (2016) A crucial role of SUMOylation in modulating Sirt6 deacetylation of H3 at lysine 56 and its tumor suppressive activity. Oncogene 35(37):4949–4956. https://doi.org/10.1038/onc.2016.24
Carafa V, Altucci L, Nebbioso A (2019) Dual tumor suppressor and tumor promoter action of sirtuins in determining malignant phenotype. Front Pharmacol 10:38. https://doi.org/10.3389/fphar.2019.00038
Cea M, Cagnetta A, Adamia S, Acharya C, Tai YT, Fulciniti M, Ohguchi H, Munshi A, Acharya P, Bhasin MK, Zhong L, Carrasco R, Monacelli F, Ballestrero A, Richardson P, Gobbi M, Lemoli RM, Munshi N, Hideshima T, Nencioni A, Chauhan D, Anderson KC (2016) Evidence for a role of the histone deacetylase SIRT6 in DNA damage response of multiple myeloma cells. Blood 127(9):1138–1150. https://doi.org/10.1182/blood-2015-06-649970
Chang AR, Ferrer CM, Mostoslavsky R (2020) SIRT6, a mammalian deacylase with multitasking abilities. Physiol Rev 100(1):145–169. https://doi.org/10.1152/physrev.00030.2018
Chen J, Zhou Y, Mueller-Steiner S, Chen LF, Kwon H, Yi S, Mucke L, Gan L (2005) SIRT1 protects against microglia-dependent amyloid-beta toxicity through inhibiting NF-kappaB signaling. J Biol Chem 280(48):40364–40374. https://doi.org/10.1074/jbc.M509329200
Chen Q, Hao W, **ao C, Wang R, Xu X, Lu H, Chen W, Deng C-X (2017) SIRT6 is essential for adipocyte differentiation by regulating mitotic clonal expansion. Cell Rep 18(13):3155–3166. https://doi.org/10.1016/j.celrep.2017.03.006
Choe M, Brusgard JL, Chumsri S, Bhandary L, Zhao XF, Lu S, Goloubeva OG, Polster BM, Fiskum GM, Girnun GD, Kim MS, Passaniti A (2015) The RUNX2 transcription factor negatively regulates SIRT6 expression to alter glucose metabolism in breast cancer cells. J Cell Biochem 116(10):2210–2226. https://doi.org/10.1002/jcb.25171
Ciccia A, Elledge SJ (2010) The DNA damage response: making it safe to play with knives. Mol Cell 40(2):179–204. https://doi.org/10.1016/j.molcel.2010.09.019
Dai H, Sinclair DA, Ellis JL, Steegborn C (2018) Sirtuin activators and inhibitors: promises, achievements, and challenges. Pharmacol Ther 188:140–154. https://doi.org/10.1016/j.pharmthera.2018.03.004
Dai M, Li L, Qin X (2019) Clinical value of miRNA-122 in the diagnosis and prognosis of various types of cancer. Oncol Lett 17(4):3919–3929. https://doi.org/10.3892/ol.2019.10024
Das C, Lucia MS, Hansen KC, Tyler JK (2009) CBP/p300-mediated acetylation of histone H3 on lysine 56. Nature 459(7243):113–117. https://doi.org/10.1038/nature07861
Dominy JE Jr, Lee Y, Jedrychowski MP, Chim H, Jurczak MJ, Camporez JP, Ruan HB, Feldman J, Pierce K, Mostoslavsky R, Denu JM, Clish CB, Yang X, Shulman GI, Gygi SP, Puigserver P (2012) The deacetylase Sirt6 activates the acetyltransferase GCN5 and suppresses hepatic gluconeogenesis. Mol Cell 48(6):900–913. https://doi.org/10.1016/j.molcel.2012.09.030
Dotto GP, Karine L (2014) miR-34a/SIRT6 in squamous differentiation and cancer. Cell Cycle 13(7):1055–1056. https://doi.org/10.4161/cc.28378
Elhanati S, Kanfi Y, Varvak A, Roichman A, Carmel-Gross I, Barth S, Gibor G, Cohen HY (2013) Multiple regulatory layers of SREBP1/2 by SIRT6. Cell Rep 4(5):905–912. https://doi.org/10.1016/j.celrep.2013.08.006
Elhanati S, Ben-Hamo R, Kanfi Y, Varvak A, Glazz R, Lerrer B, Efroni S, Cohen HY (2016) Reciprocal regulation between SIRT6 and miR-122 controls liver metabolism and predicts hepatocarcinoma prognosis. Cell Rep 14(2):234–242. https://doi.org/10.1016/j.celrep.2015.12.023
Feldman JL, Baeza J, Denu JM (2013) Activation of the protein deacetylase SIRT6 by long-chain fatty acids and widespread deacylation by mammalian sirtuins. J Biol Chem 288(43):31350–31356. https://doi.org/10.1074/jbc.C113.511261
Fiorentino F, Carafa V, Favale G, Altucci L, Mai A, Rotili D (2021) The two-faced role of SIRT6 in cancer. Cancers (Basel) 13(5):1156. https://doi.org/10.3390/cancers13051156
Fong MY, Zhou W, Liu L, Alontaga AY, Chandra M, Ashby J, Chow A, O’Connor STF, Li S, Chin AR, Somlo G, Palomares M, Li Z, Tremblay JR, Tsuyada A, Sun G, Reid MA, Wu X, Swiderski P, Ren X, Shi Y, Kong M, Zhong W, Chen Y, Wang SE (2015) Breast-cancer-secreted miR-122 reprograms glucose metabolism in premetastatic niche to promote metastasis. Nature Cell Biol 17(2):183–194. https://doi.org/10.1038/ncb3094
Gao C, Wei J, Tang T, Huang Z (2020) Role of microRNA-33a in malignant cells (Review). Oncol Lett 20(3):2537–2556. https://doi.org/10.3892/ol.2020.11835
Geng Q, Peng H, Chen F, Luo R, Li R (2015) High expression of Sirt7 served as a predictor of adverse outcome in breast cancer. Int J Clin Exp Pathol 8(2):1938–1945
Ghosh S, Liu B, Wang Y, Hao Q, Zhou Z (2015) Lamin A is an endogenous SIRT6 activator and promotes SIRT6-mediated DNA repair. Cell Rep 13(7):1396–1406. https://doi.org/10.1016/j.celrep.2015.10.006
Gil R, Barth S, Kanfi Y, Cohen HY (2013) SIRT6 exhibits nucleosome-dependent deacetylase activity. Nucleic Acids Res 41(18):8537–8545. https://doi.org/10.1093/nar/gkt642
Ha SY, Yu JI, Choi C, Kang SY, Joh J-W, Paik SW, Kim S, Kim M, Park HC, Park C-K (2019) Prognostic significance of miR-122 expression after curative resection in patients with hepatocellular carcinoma. Sci Rep 9(1):14738. https://doi.org/10.1038/s41598-019-50594-2
Haigis MC, Mostoslavsky R, Haigis KM, Fahie K, Christodoulou DC, Murphy AJ, Valenzuela DM, Yancopoulos GD, Karow M, Blander G, Wolberger C, Prolla TA, Weindruch R, Alt FW, Guarente L (2006) SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta cells. Cell 126(5):941–954. https://doi.org/10.1016/j.cell.2006.06.057
Hall JA, Dominy JE, Lee Y, Puigserver P (2013) The sirtuin family’s role in aging and age-associated pathologies. J Clin Invest 123(3):973–979. https://doi.org/10.1172/JCI64094
Hallows WC, Lee S, Denu JM (2006) Sirtuins deacetylate and activate mammalian acetyl-CoA synthetases. Proc Natl Acad Sci U S A 103(27):10230–10235. https://doi.org/10.1073/pnas.0604392103
Han LL, Jia L, Wu F, Huang C (2019) Sirtuin6 (SIRT6) promotes the EMT of hepatocellular carcinoma by stimulating autophagic degradation of e-cadherin. Mol Cancer Res 17(11):2267–2280. https://doi.org/10.1158/1541-7786.MCR-19-0321
Hassanieh S, Mostoslavsky R (2018) Chapter 9 - multitasking roles of the mammalian deacetylase SIRT6. In: Guarente L, Mostoslavsky R, Kazantsev A (eds) Introductory review on sirtuins in biology, aging, and disease. Academic Press, Cambridge, MA, pp 117–130. https://doi.org/10.1016/B978-0-12-813499-3.00009-5
He B, Hu J, Zhang X, Lin H (2014) Thiomyristoyl peptides as cell-permeable Sirt6 inhibitors. Org Biomol Chem 12(38):7498–7502. https://doi.org/10.1039/c4ob00860j
He T, Shang J, Gao C, Guan X, Chen Y, Zhu L, Zhang L, Zhang C, Zhang J, Pang T (2020) A novel SIRT6 activator ameliorates neuroinflammation and ischemic brain injury via EZH2/FOXC1 axis. Acta Pharm Sin B. 11(3):708–726. https://doi.org/10.1016/j.apsb.2020.11.002
Heger V, Tyni J, Hunyadi A, Horáková L, Lahtela-Kakkonen M, Rahnasto-Rilla M (2019) Quercetin based derivatives as sirtuin inhibitors. Biomed Pharmacother 111:1326–1333. https://doi.org/10.1016/j.biopha.2019.01.035
Hida Y, Kubo Y, Murao K, Arase S (2007) Strong expression of a longevity-related protein, SIRT1, in Bowen’s disease. Arch Dermatol Res 299(2):103–106. https://doi.org/10.1007/s00403-006-0725-6
Hiratsuka M, Inoue T, Toda T, Kimura N, Shirayoshi Y, Kamitani H, Watanabe T, Ohama E, Tahimic CG, Kurimasa A, Oshimura M (2003) Proteomics-based identification of differentially expressed genes in human gliomas: down-regulation of SIRT2 gene. Biochem Biophys Res Commun 309(3):558–566. https://doi.org/10.1016/j.bbrc.2003.08.029
Huang JY, Hirschey MD, Shimazu T, Ho L, Verdin E (2010) Mitochondrial sirtuins. Biochim Biophys Acta 1804(8):1645–1651. https://doi.org/10.1016/j.bbapap.2009.12.021
Huang Z, Zhao J, Deng W, Chen Y, Shang J, Song K, Zhang L, Wang C, Lu S, Yang X, He B, Min J, Hu H, Tan M, Xu J, Zhang Q, Zhong J, Sun X, Mao Z, Lin H, **ao M, Chin YE, Jiang H, Xu Y, Chen G, Zhang J (2018) Identification of a cellularly active SIRT6 allosteric activator. Nat Chem Biol 14(12):1118–1126. https://doi.org/10.1038/s41589-018-0150-0
Huffman DM, Grizzle WE, Bamman MM, Kim JS, Eltoum IA, Elgavish A, Nagy TR (2007) SIRT1 is significantly elevated in mouse and human prostate cancer. Cancer Res 67(14):6612–6618. https://doi.org/10.1158/0008-5472.CAN-07-0085
Iachettini S, Trisciuoglio D, Rotili D, Lucidi A, Salvati E, Zizza P, Di Leo L, Del Bufalo D, Ciriolo MR, Leonetti C, Steegborn C, Mai A, Rizzo A, Biroccio A (2018) Pharmacological activation of SIRT6 triggers lethal autophagy in human cancer cells. Cell Death & Disease 9(10):996. https://doi.org/10.1038/s41419-018-1065-0
Inoue T, Hiratsuka M, Osaki M, Yamada H, Kishimoto I, Yamaguchi S, Nakano S, Katoh M, Ito H, Oshimura M (2007) SIRT2, a tubulin deacetylase, acts to block the entry to chromosome condensation in response to mitotic stress. Oncogene 26(7):945–957. https://doi.org/10.1038/sj.onc.1209857
Ioris RM, Galie M, Ramadori G, Anderson JG, Charollais A, Konstantinidou G, Brenachot X, Aras E, Goga A, Ceglia N, Sebastian C, Martinvalet D, Mostoslavsky R, Baldi P, Coppari R (2017) SIRT6 suppresses cancer stem-like capacity in tumors with PI3K activation independently of its deacetylase activity. Cell Rep 18(8):1858–1868. https://doi.org/10.1016/j.celrep.2017.01.065
Jedrusik-Bode M, Studencka M, Smolka C, Baumann T, Schmidt H, Kampf J, Paap F, Martin S, Tazi J, Muller KM, Kruger M, Braun T, Bober E (2013) The sirtuin SIRT6 regulates stress granule formation in C. elegans and mammals. J Cell Sci 126(Pt 22):5166–5177. https://doi.org/10.1242/jcs.130708
Jeong SM, Lee A, Lee J, Haigis MC (2014) SIRT4 protein suppresses tumor formation in genetic models of Myc-induced B cell lymphoma. J Biol Chem 289(7):4135–4144. https://doi.org/10.1074/jbc.M113.525949
Jiang H, Khan S, Wang Y, Charron G, He B, Sebastian C, Du J, Kim R, Ge E, Mostoslavsky R, Hang HC, Hao Q, Lin H (2013) SIRT6 regulates TNF-alpha secretion through hydrolysis of long-chain fatty acyl lysine. Nature 496(7443):110–113. https://doi.org/10.1038/nature12038
Kaeberlein M, McVey M, Guarente L (1999) The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Genes Dev 13(19):2570–2580. https://doi.org/10.1101/gad.13.19.2570
Kanfi Y, Peshti V, Gil R, Naiman S, Nahum L, Levin E, Kronfeld-Schor N, Cohen HY (2010) SIRT6 protects against pathological damage caused by diet-induced obesity. Aging Cell 9(2):162–173. https://doi.org/10.1111/j.1474-9726.2009.00544.x
Kanfi Y, Naiman S, Amir G, Peshti V, Zinman G, Nahum L, Bar-Joseph Z, Cohen HY (2012) The sirtuin SIRT6 regulates lifespan in male mice. Nature 483(7388):218–221. https://doi.org/10.1038/nature10815
Khan D, Sarikhani M, Dasgupta S, Maniyadath B, Pandit AS, Mishra S, Ahamed F, Dubey A, Fathma N, Atreya HS, Kolthur-Seetharam U, Sundaresan NR (2018) SIRT6 deacetylase transcriptionally regulates glucose metabolism in heart. J Cell Physiol 233(7):5478–5489. https://doi.org/10.1002/jcp.26434
Khan D, Ara T, Ravi V, Rajagopal R, Tandon H, Parvathy J, Gonzalez EA, Asirvatham-Jeyaraj N, Krishna S, Mishra S, Raghu S, Bhati AS, Tamta AK, Dasgupta S, Kolthur-Seetharam U, Etchegaray JP, Mostoslavsky R, Rao PSM, Srinivasan N, Sundaresan NR (2021) SIRT6 transcriptionally regulates fatty acid transport by suppressing PPARγ. Cell Rep 35(9):109190. https://doi.org/10.1016/j.celrep.2021.109190
Khongkow M, Olmos Y, Gong C, Gomes AR, Monteiro LJ, Yague E, Cavaco TB, Khongkow P, Man EP, Laohasinnarong S, Koo CY, Harada-Shoji N, Tsang JW, Coombes RC, Schwer B, Khoo US, Lam EW (2013) SIRT6 modulates paclitaxel and epirubicin resistance and survival in breast cancer. Carcinogenesis 34(7):1476–1486. https://doi.org/10.1093/carcin/bgt098
Kim HS, Patel K, Muldoon-Jacobs K, Bisht KS, Aykin-Burns N, Pennington JD, van der Meer R, Nguyen P, Savage J, Owens KM, Vassilopoulos A, Ozden O, Park SH, Singh KK, Abdulkadir SA, Spitz DR, Deng CX, Gius D (2010a) SIRT3 is a mitochondria-localized tumor suppressor required for maintenance of mitochondrial integrity and metabolism during stress. Cancer Cell 17(1):41–52. https://doi.org/10.1016/j.ccr.2009.11.023
Kim HS, **ao C, Wang RH, Lahusen T, Xu X, Vassilopoulos A, Vazquez-Ortiz G, Jeong WI, Park O, Ki SH, Gao B, Deng CX (2010b) Hepatic-specific disruption of SIRT6 in mice results in fatty liver formation due to enhanced glycolysis and triglyceride synthesis. Cell Metab 12(3):224–236. https://doi.org/10.1016/j.cmet.2010.06.009
Kim JK, Noh JH, Jung KH, Eun JW, Bae HJ, Kim MG, Chang YG, Shen Q, Park WS, Lee JY, Borlak J, Nam SW (2013) Sirtuin7 oncogenic potential in human hepatocellular carcinoma and its regulation by the tumor suppressors MiR-125a-5p and MiR-125b. Hepatology 57(3):1055–1067. https://doi.org/10.1002/hep.26101
Kim JH, Lee JM, Kim JH, Kim KR (2018) Fluvastatin activates sirtuin 6 to regulate sterol regulatory element-binding proteins and AMP-activated protein kinase in HepG2 cells. Biochem Biophys Res Commun 503(3):1415–1421. https://doi.org/10.1016/j.bbrc.2018.07.057
Klein MA, Liu C, Kuznetsov VI, Feltenberger JB, Tang W, Denu JM (2020) Mechanism of activation for the sirtuin 6 protein deacylase. J Biol Chem 295(5):1385–1399. https://doi.org/10.1074/jbc.RA119.011285
Kokkonen P, Rahnasto-Rilla M, Kiviranta PH, Huhtiniemi T, Laitinen T, Poso A, Jarho E, Lahtela-Kakkonen M (2012) Peptides and pseudopeptides as SIRT6 deacetylation inhibitors. ACS Med Chem Lett 3(12):969–974. https://doi.org/10.1021/ml300139n
Kuang J, Zhang Y, Liu Q, Shen J, Pu S, Cheng S, Chen L, Li H, Wu T, Li R, Li Y, Zou M, Zhang Z, Jiang W, Xu G, Qu A, **e W, He J (2017) Fat-specific Sirt6 ablation sensitizes mice to high-fat diet-induced obesity and insulin resistance by inhibiting lipolysis. Diabetes 66(5):1159–1171. https://doi.org/10.2337/db16-1225
Kugel S, Mostoslavsky R (2014) Chromatin and beyond: the multitasking roles for SIRT6. Trends Biochem Sci 39(2):72–81. https://doi.org/10.1016/j.tibs.2013.12.002
Kugel S, Feldman JL, Klein MA, Silberman DM, Sebastian C, Mermel C, Dobersch S, Clark AR, Getz G, Denu JM, Mostoslavsky R (2015) Identification of and molecular basis for SIRT6 loss-of-function point mutations in cancer. Cell Rep 13(3):479–488. https://doi.org/10.1016/j.celrep.2015.09.022
Kugel S, Sebastian C, Fitamant J, Ross KN, Saha SK, Jain E, Gladden A, Arora KS, Kato Y, Rivera MN, Ramaswamy S, Sadreyev RI, Goren A, Deshpande V, Bardeesy N, Mostoslavsky R (2016) SIRT6 suppresses pancreatic cancer through control of Lin28b. Cell 165(6):1401–1415. https://doi.org/10.1016/j.cell.2016.04.033
Lee N, Ryu HG, Kwon JH, Kim DK, Kim SR, Wang HJ, Kim KT, Choi KY (2016) SIRT6 depletion suppresses tumor growth by promoting cellular senescence induced by DNA damage in HCC. PLoS One 11(11):e0165835. https://doi.org/10.1371/journal.pone.0165835
Lerrer B, Gertler AA, Cohen HY (2016) The complex role of SIRT6 in carcinogenesis. Carcinogenesis 37(2):108–118. https://doi.org/10.1093/carcin/bgv167
Lin Z, Yang H, Tan C, Li J, Liu Z, Quan Q, Kong S, Ye J, Gao B, Fang D (2013) USP10 antagonizes c-Myc transcriptional activation through SIRT6 stabilization to suppress tumor formation. Cell Rep 5(6):1639–1649. https://doi.org/10.1016/j.celrep.2013.11.029
Lin Y, Liu AY, Fan C, Zheng H, Li Y, Zhang C, Wu S, Yu D, Huang Z, Liu F, Luo Q, Yang CJ, Ouyang G (2015) MicroRNA-33b Inhibits Breast Cancer Metastasis by Targeting HMGA2, SALL4 and Twist1. Sci Rep 5:9995. https://doi.org/10.1038/srep09995
Liszt G, Ford E, Kurtev M, Guarente L (2005) Mouse Sir2 homolog SIRT6 is a nuclear ADP-ribosyltransferase. J Biol Chem 280(22):21313–21320. https://doi.org/10.1074/jbc.M413296200
Liu Y, **e QR, Wang B, Shao J, Zhang T, Liu T, Huang G, **a W (2013) Inhibition of SIRT6 in prostate cancer reduces cell viability and increases sensitivity to chemotherapeutics. Protein Cell 4(9):702–710. https://doi.org/10.1007/s13238-013-3054-5
Liu W, Wu M, Du H, Shi X, Zhang T, Li J (2018) SIRT6 inhibits colorectal cancer stem cell proliferation by targeting CDC25A. Oncol Lett 15(4):5368–5374. https://doi.org/10.3892/ol.2018.7989
Lu W, Zuo Y, Feng Y, Zhang M (2014) SIRT5 facilitates cancer cell growth and drug resistance in non-small cell lung cancer. Tumour Biol 35(11):10699–10705. https://doi.org/10.1007/s13277-014-2372-4
Mao Z, Hine C, Tian X, Van Meter M, Au M, Vaidya A, Seluanov A, Gorbunova V (2011) SIRT6 promotes DNA repair under stress by activating PARP1. Science 332(6036):1443–1446. https://doi.org/10.1126/science.1202723
Masri S, Rigor P, Cervantes M, Ceglia N, Sebastian C, **ao C, Roqueta-Rivera M, Deng C, Osborne TF, Mostoslavsky R, Baldi P, Sassone-Corsi P (2014) Partitioning circadian transcription by SIRT6 leads to segregated control of cellular metabolism. Cell 158(3):659–672. https://doi.org/10.1016/j.cell.2014.06.050
Merksamer PI, Liu Y, He W, Hirschey MD, Chen D, Verdin E (2013) The sirtuins, oxidative stress and aging: an emerging link. Aging (Albany NY) 5(3):144–150. https://doi.org/10.18632/aging.100544
Michishita E, Park JY, Burneskis JM, Barrett JC, Horikawa I (2005) Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins. Mol Biol Cell 16(10):4623–4635. https://doi.org/10.1091/mbc.e05-01-0033
Michishita E, McCord RA, Berber E, Kioi M, Padilla-Nash H, Damian M, Cheung P, Kusumoto R, Kawahara TL, Barrett JC, Chang HY, Bohr VA, Ried T, Gozani O, Chua KF (2008) SIRT6 is a histone H3 lysine 9 deacetylase that modulates telomeric chromatin. Nature 452(7186):492–496. https://doi.org/10.1038/nature06736
Michishita E, McCord RA, Boxer LD, Barber MF, Hong T, Gozani O, Chua KF (2009) Cell cycle-dependent deacetylation of telomeric histone H3 lysine K56 by human SIRT6. Cell Cycle 8(16):2664–2666. https://doi.org/10.4161/cc.8.16.9367
Milne JC, Lambert PD, Schenk S, Carney DP, Smith JJ, Gagne DJ, ** L, Boss O, Perni RB, Vu CB, Bemis JE, **e R, Disch JS, Ng PY, Nunes JJ, Lynch AV, Yang H, Galonek H, Israelian K, Choy W, Iffland A, Lavu S, Medvedik O, Sinclair DA, Olefsky JM, Jirousek MR, Elliott PJ, Westphal CH (2007) Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes. Nature 450(7170):712–716. https://doi.org/10.1038/nature06261
Min L, Ji Y, Bakiri L, Qiu Z, Cen J, Chen X, Chen L, Scheuch H, Zheng H, Qin L, Zatloukal K, Hui L, Wagner EF (2012) Liver cancer initiation is controlled by AP-1 through SIRT6-dependent inhibition of survivin. Nat Cell Biol 14(11):1203–1211. https://doi.org/10.1038/ncb2590
Ming M, Han W, Zhao B, Sundaresan NR, Deng CX, Gupta MP, He YY (2014) SIRT6 promotes COX-2 expression and acts as an oncogene in skin cancer. Cancer Res 74(20):5925–5933. https://doi.org/10.1158/0008-5472.CAN-14-1308
Miyo M, Yamamoto H, Konno M, Colvin H, Nishida N, Koseki J, Kawamoto K, Ogawa H, Hamabe A, Uemura M, Nishimura J, Hata T, Takemasa I, Mizushima T, Doki Y, Mori M, Ishii H (2015) Tumour-suppressive function of SIRT4 in human colorectal cancer. Br J Cancer 113(3):492–499. https://doi.org/10.1038/bjc.2015.226
Mostoslavsky R, Chua KF, Lombard DB, Pang WW, Fischer MR, Gellon L, Liu P, Mostoslavsky G, Franco S, Murphy MM, Mills KD, Patel P, Hsu JT, Hong AL, Ford E, Cheng HL, Kennedy C, Nunez N, Bronson R, Frendewey D, Auerbach W, Valenzuela D, Karow M, Hottiger MO, Hursting S, Barrett JC, Guarente L, Mulligan R, Demple B, Yancopoulos GD, Alt FW (2006) Genomic instability and aging-like phenotype in the absence of mammalian SIRT6. Cell 124(2):315–329. https://doi.org/10.1016/j.cell.2005.11.044
Nishida Y, Rardin MJ, Carrico C, He W, Sahu AK, Gut P, Najjar R, Fitch M, Hellerstein M, Gibson BW, Verdin E (2015) SIRT5 regulates both cytosolic and mitochondrial protein malonylation with glycolysis as a major target. Mol Cell 59(2):321–332. https://doi.org/10.1016/j.molcel.2015.05.022
North BJ, Verdin E (2007) Interphase nucleo-cytoplasmic shuttling and localization of SIRT2 during mitosis. PLoS One 2(8):e784. https://doi.org/10.1371/journal.pone.0000784
Pan PW, Feldman JL, Devries MK, Dong A, Edwards AM, Denu JM (2011) Structure and biochemical functions of SIRT6. J Biol Chem 286(16):14575–14587. https://doi.org/10.1074/jbc.M111.218990
Pan H, Guan D, Liu X, Li J, Wang L, Wu J, Zhou J, Zhang W, Ren R, Zhang W, Li Y, Yang J, Hao Y, Yuan T, Yuan G, Wang H, Ju Z, Mao Z, Li J, Qu J, Tang F, Liu GH (2016) SIRT6 safeguards human mesenchymal stem cells from oxidative stress by coactivating NRF2. Cell Res 26(2):190–205. https://doi.org/10.1038/cr.2016.4
Paredes S, Villanova L, Chua KF (2014) Molecular pathways: emerging roles of mammalian Sirtuin SIRT7 in cancer. Clin Cancer Res 20(7):1741–1746. https://doi.org/10.1158/1078-0432.CCR-13-1547
Parenti MD, Grozio A, Bauer I, Galeno L, Damonte P, Millo E, Sociali G, Franceschi C, Ballestrero A, Bruzzone S, Del Rio A, Nencioni A (2014) Discovery of novel and selective SIRT6 inhibitors. J Med Chem 57(11):4796–4804. https://doi.org/10.1021/jm500487d
Park J, Chen Y, Tishkoff DX, Peng C, Tan M, Dai L, **e Z, Zhang Y, Zwaans BM, Skinner ME, Lombard DB, Zhao Y (2013) SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways. Mol Cell 50(6):919–930. https://doi.org/10.1016/j.molcel.2013.06.001
Peng C, Lu Z, **e Z, Cheng Z, Chen Y, Tan M, Luo H, Zhang Y, He W, Yang K, Zwaans BM, Tishkoff D, Ho L, Lombard D, He TC, Dai J, Verdin E, Ye Y, Zhao Y (2011) The first identification of lysine malonylation substrates and its regulatory enzyme. Mol Cell Proteomics 10(12):M111.012658. https://doi.org/10.1074/mcp.M111.012658
Peshti V, Obolensky A, Nahum L, Kanfi Y, Rathaus M, Avraham M, Tinman S, Alt FW, Banin E, Cohen HY (2017) Characterization of physiological defects in adult SIRT6-/- mice. PLoS One 12(4):e0176371. https://doi.org/10.1371/journal.pone.0176371
Qin K, Zhang N, Zhang Z, Nipper M, Zhu Z, Leighton J, Xu K, Musi N, Wang P (2018) SIRT6-mediated transcriptional suppression of Txnip is critical for pancreatic beta cell function and survival in mice. Diabetologia 61(4):906–918. https://doi.org/10.1007/s00125-017-4542-6
Qiu X, Brown K, Hirschey MD, Verdin E, Chen D (2010) Calorie restriction reduces oxidative stress by SIRT3-mediated SOD2 activation. Cell Metab 12(6):662–667. https://doi.org/10.1016/j.cmet.2010.11.015
Rahnasto-Rilla M, Kokkola T, Jarho E, Lahtela-Kakkonen M, Moaddel R (2016) N-Acylethanolamines bind to SIRT6. Chembiochem 17(1):77–81. https://doi.org/10.1002/cbic.201500482
Rahnasto-Rilla MK, McLoughlin P, Kulikowicz T, Doyle M, Bohr VA, Lahtela-Kakkonen M, Ferrucci L, Hayes M, Moaddel R (2017) The identification of a SIRT6 activator from brown algae fucus distichus. Mar Drugs 15(6):190. https://doi.org/10.3390/md15060190
Rahnasto-Rilla M, Tyni J, Huovinen M, Jarho E, Kulikowicz T, Ravichandran S, Vilhelm AB, Ferrucci L, Lahtela-Kakkonen M, Moaddel R (2018) Natural polyphenols as sirtuin 6 modulators. Sci Rep 8(1):4163. https://doi.org/10.1038/s41598-018-22388-5
Ravi V, Jain A, Khan D, Ahamed F, Mishra S, Giri M, Inbaraj M, Krishna S, Sarikhani M, Maity S, Kumar S, Shah RA, Dave P, Pandit AS, Rajendran R, Desingu PA, Varshney U, Das S, Kolthur-Seetharam U, Rajakumari S, Singh M, Sundaresan NR (2019) SIRT6 transcriptionally regulates global protein synthesis through transcription factor Sp1 independent of its deacetylase activity. Nucleic Acids Res 47(17):9115–9131. https://doi.org/10.1093/nar/gkz648
Rine J, Strathern JN, Hicks JB, Herskowitz I (1979) A suppressor of mating-type locus mutations in Saccharomyces cerevisiae: evidence for and identification of cryptic mating-type loci. Genetics 93(4):877–901
Rizzo A, Iachettini S, Salvati E, Zizza P, Maresca C, D’Angelo C, Benarroch-Popivker D, Capolupo A, Del Gaudio F, Cosconati S, Di Maro S, Merlino F, Novellino E, Amoreo CA, Mottolese M, Sperduti I, Gilson E, Biroccio A (2017) SIRT6 interacts with TRF2 and promotes its degradation in response to DNA damage. Nucleic Acids Res 45(4):1820–1834. https://doi.org/10.1093/nar/gkw1202
Rogina B, Helfand SL (2004) Sir2 mediates longevity in the fly through a pathway related to calorie restriction. Proc Natl Acad Sci U S A 101(45):15998–16003. https://doi.org/10.1073/pnas.0404184101
Ronnebaum SM, Wu Y, McDonough H, Patterson C (2013) The ubiquitin ligase CHIP prevents SirT6 degradation through noncanonical ubiquitination. Mol Cell Biol 33(22):4461–4472. https://doi.org/10.1128/MCB.00480-13
Schumacker PT (2010) A tumor suppressor SIRTainty. Cancer Cell 17(1):5–6. https://doi.org/10.1016/j.ccr.2009.12.032
Sebastian C, Zwaans BM, Silberman DM, Gymrek M, Goren A, Zhong L, Ram O, Truelove J, Guimaraes AR, Toiber D, Cosentino C, Greenson JK, MacDonald AI, McGlynn L, Maxwell F, Edwards J, Giacosa S, Guccione E, Weissleder R, Bernstein BE, Regev A, Shiels PG, Lombard DB, Mostoslavsky R (2012) The histone deacetylase SIRT6 is a tumor suppressor that controls cancer metabolism. Cell 151(6):1185–1199. https://doi.org/10.1016/j.cell.2012.10.047
Singh N, Ravichandran S, Spelman K, Fugmann SD, Moaddel R (2014) The identification of a novel SIRT6 modulator from Trigonella foenum-graecum using ligand fishing with protein coated magnetic beads. J Chromatogr B Analyt Technol Biomed Life Sci 968:105–111. https://doi.org/10.1016/j.jchromb.2014.03.016
Singh CK, Chhabra G, Ndiaye MA, Garcia-Peterson LM, Mack NJ, Ahmad N (2018) The role of sirtuins in antioxidant and redox signaling. Antioxid Redox Signal 28(8):643–661. https://doi.org/10.1089/ars.2017.7290
Sociali G, Galeno L, Parenti MD, Grozio A, Bauer I, Passalacqua M, Boero S, Donadini A, Millo E, Bellotti M, Sturla L, Damonte P, Puddu A, Ferroni C, Varchi G, Franceschi C, Ballestrero A, Poggi A, Bruzzone S, Nencioni A, Del Rio A (2015) Quinazolinedione SIRT6 inhibitors sensitize cancer cells to chemotherapeutics. Eur J Med Chem 102:530–539. https://doi.org/10.1016/j.ejmech.2015.08.024
Sociali G, Magnone M, Ravera S, Damonte P, Vigliarolo T, Von Holtey M, Vellone VG, Millo E, Caffa I, Cea M, Parenti MD, Del Rio A, Murone M, Mostoslavsky R, Grozio A, Nencioni A, Bruzzone S (2017) Pharmacological Sirt6 inhibition improves glucose tolerance in a type 2 diabetes mouse model. FASEB J 31(7):3138–3149. https://doi.org/10.1096/fj.201601294R
Stunkel W, Peh BK, Tan YC, Nayagam VM, Wang X, Salto-Tellez M, Ni B, Entzeroth M, Wood J (2007) Function of the SIRT1 protein deacetylase in cancer. Biotechnol J 2(11):1360–1368. https://doi.org/10.1002/biot.200700087
Sundaresan NR, Vasudevan P, Zhong L, Kim G, Samant S, Parekh V, Pillai VB, Ravindra PV, Gupta M, Jeevanandam V, Cunningham JM, Deng CX, Lombard DB, Mostoslavsky R, Gupta MP (2012) The sirtuin SIRT6 blocks IGF-Akt signaling and development of cardiac hypertrophy by targeting c-Jun. Nat Med 18(11):1643–1650. https://doi.org/10.1038/nm.2961
Tanno M, Sakamoto J, Miura T, Shimamoto K, Horio Y (2007) Nucleocytoplasmic shuttling of the NAD+-dependent histone deacetylase SIRT1. J Biol Chem 282(9):6823–6832. https://doi.org/10.1074/jbc.M609554200
Tao R, **ong X, DePinho RA, Deng CX, Dong XC (2013) Hepatic SREBP-2 and cholesterol biosynthesis are regulated by FoxO3 and Sirt6. J Lipid Res 54(10):2745–2753. https://doi.org/10.1194/jlr.M039339
Tasselli L, ** Y, Zheng W, Tennen RI, Odrowaz Z, Simeoni F, Li W, Chua KF (2016) SIRT6 deacetylates H3K18ac at pericentric chromatin to prevent mitotic errors and cellular senescence. Nature Struct Mol Biol 23(5):434–440. https://doi.org/10.1038/nsmb.3202
Tenhunen J, Kucera T, Huovinen M, Kublbeck J, Bisenieks E, Vigante B, Ogle Z, Duburs G, Dolezal M, Moaddel R, Lahtela-Kakkonen M, Rahnasto-Rilla M (2021) Screening of SIRT6 inhibitors and activators: A novel activator has an impact on breast cancer cells. Biomed Pharmacother 138:111452. https://doi.org/10.1016/j.biopha.2021.111452
Thirumurthi U, Shen J, **a W, LaBaff AM, Wei Y, Li CW, Chang WC, Chen CH, Lin HK, Yu D, Hung MC (2014) MDM2-mediated degradation of SIRT6 phosphorylated by AKT1 promotes tumorigenesis and trastuzumab resistance in breast cancer. Sci Signal 7(336):ra71. https://doi.org/10.1126/scisignal.2005076
Timucin AC, Basaga H (2016) SIRT6 is a positive regulator of aldose reductase expression in U937 and HeLa cells under osmotic stress: in vitro and in silico insights. PLoS One 11(8):e0161494. https://doi.org/10.1371/journal.pone.0161494
Toiber D, Erdel F, Bouazoune K, Silberman DM, Zhong L, Mulligan P, Sebastian C, Cosentino C, Martinez-Pastor B, Giacosa S, D’Urso A, Naar AM, Kingston R, Rippe K, Mostoslavsky R (2013) SIRT6 recruits SNF2H to DNA break sites, preventing genomic instability through chromatin remodeling. Mol Cell 51(4):454–468. https://doi.org/10.1016/j.molcel.2013.06.018
Tong L, Denu JM (2010) Function and metabolism of sirtuin metabolite O-acetyl-ADP-ribose. Biochim Biophys Acta 1804(8):1617–1625. https://doi.org/10.1016/j.bbapap.2010.02.007
Van Meter M, Mao Z, Gorbunova V, Seluanov A (2011) SIRT6 overexpression induces massive apoptosis in cancer cells but not in normal cells. Cell Cycle 10(18):3153–3158. https://doi.org/10.4161/cc.10.18.17435
Van Meter M, Kashyap M, Rezazadeh S, Geneva AJ, Morello TD, Seluanov A, Gorbunova V (2014) SIRT6 represses LINE1 retrotransposons by ribosylating KAP1 but this repression fails with stress and age. Nat Commun 5:5011. https://doi.org/10.1038/ncomms6011
Van Meter M, Simon M, Tombline G, May A, Morello TD, Hubbard BP, Bredbenner K, Park R, Sinclair DA, Bohr VA, Gorbunova V, Seluanov A (2016) JNK Phosphorylates SIRT6 to stimulate DNA double-strand break repair in response to oxidative stress by recruiting PARP1 to DNA breaks. Cell Rep 16(10):2641–2650. https://doi.org/10.1016/j.celrep.2016.08.006
Wang RH, Sengupta K, Li C, Kim HS, Cao L, **ao C, Kim S, Xu X, Zheng Y, Chilton B, Jia R, Zheng ZM, Appella E, Wang XW, Ried T, Deng CX (2008) Impaired DNA damage response, genome instability, and tumorigenesis in SIRT1 mutant mice. Cancer Cell 14(4):312–323. https://doi.org/10.1016/j.ccr.2008.09.001
Wang YP, Zhou LS, Zhao YZ, Wang SW, Chen LL, Liu LX, Ling ZQ, Hu FJ, Sun YP, Zhang JY, Yang C, Yang Y, **ong Y, Guan KL, Ye D (2014) Regulation of G6PD acetylation by SIRT2 and KAT9 modulates NADPH homeostasis and cell survival during oxidative stress. EMBO J 33(12):1304–1320. https://doi.org/10.1002/embj.201387224
Wang Y, Pan T, Wang H, Li L, Li J, Zhang D, Yang H (2017) Overexpression of SIRT6 attenuates the tumorigenicity of hepatocellular carcinoma cells. Oncotarget 8(44):76223–76230. https://doi.org/10.18632/oncotarget.19297
Wencel PL, Lukiw WJ, Strosznajder JB, Strosznajder RP (2018) Inhibition of Poly(ADP-ribose) Polymerase-1 Enhances Gene Expression of Selected Sirtuins and APP Cleaving Enzymes in Amyloid Beta Cytotoxicity. Mol Neurobiol 55(6):4612–4623. https://doi.org/10.1007/s12035-017-0646-8
Wood M, Rymarchyk S, Zheng S, Cen Y (2018) Trichostatin A inhibits deacetylation of histone H3 and p53 by SIRT6. Arch Biochem Biophys 638:8–17. https://doi.org/10.1016/j.abb.2017.12.009
Wu M, Seto E, Zhang J (2015) E2F1 enhances glycolysis through suppressing Sirt6 transcription in cancer cells. Oncotarget 6(13):11252–11263. https://doi.org/10.18632/oncotarget.3594
Wushou A, Hou J, Zhao YJ, Shao ZM (2014) Twist-1 up-regulation in carcinoma correlates to poor survival. Int J Mol Sci 15(12):21621–21630. https://doi.org/10.3390/ijms151221621
**ao C, Kim HS, Lahusen T, Wang RH, Xu X, Gavrilova O, Jou W, Gius D, Deng CX (2010) SIRT6 deficiency results in severe hypoglycemia by enhancing both basal and insulin-stimulated glucose uptake in mice. J Biol Chem 285(47):36776–36784. https://doi.org/10.1074/jbc.M110.168039
**ao C, Wang RH, Lahusen TJ, Park O, Bertola A, Maruyama T, Reynolds D, Chen Q, Xu X, Young HA, Chen WJ, Gao B, Deng CX (2012) Progression of chronic liver inflammation and fibrosis driven by activation of c-JUN signaling in Sirt6 mutant mice. J Biol Chem 287(50):41903–41913. https://doi.org/10.1074/jbc.M112.415182
**ong X, Sun X, Wang Q, Qian X, Zhang Y, Pan X, Dong XC (2016) SIRT6 protects against palmitate-induced pancreatic β-cell dysfunction and apoptosis. J Endocrinol 231(2):159–165. https://doi.org/10.1530/joe-16-0317
**ong X, Zhang C, Zhang Y, Fan R, Qian X, Dong XC (2017) Fabp4-Cre-mediated Sirt6 deletion impairs adipose tissue function and metabolic homeostasis in mice. J Endocrinol 233(3):307–314. https://doi.org/10.1530/JOE-17-0033
Xu Y, Li F, Lv L, Li T, Zhou X, Deng CX, Guan KL, Lei QY, **ong Y (2014) Oxidative stress activates SIRT2 to deacetylate and stimulate phosphoglycerate mutase. Cancer Res 74(13):3630–3642. https://doi.org/10.1158/0008-5472.CAN-13-3615
Xu Z, Zhang L, Zhang W, Meng D, Zhang H, Jiang Y, Xu X, Van Meter M, Seluanov A, Gorbunova V, Mao Z (2015) SIRT6 rescues the age related decline in base excision repair in a PARP1-dependent manner. Cell Cycle 14(2):269–276. https://doi.org/10.4161/15384101.2014.980641
Yamamoto H, Schoonjans K, Auwerx J (2007) Sirtuin functions in health and disease. Mol Endocrinol 21(8):1745–1755. https://doi.org/10.1210/me.2007-0079
Yang B, Zwaans BM, Eckersdorff M, Lombard DB (2009) The sirtuin SIRT6 deacetylates H3 K56Ac in vivo to promote genomic stability. Cell Cycle 8(16):2662–2663. https://doi.org/10.4161/cc.8.16.9329
Yao L, Cui X, Chen Q, Yang X, Fang F, Zhang J, Liu G, ** W, Chang Y (2017) Cold-inducible SIRT6 regulates thermogenesis of brown and beige fat. Cell Rep 20(3):641–654. https://doi.org/10.1016/j.celrep.2017.06.069
Yu H, Ye W, Wu J, Meng X, Liu RY, Ying X, Zhou Y, Wang H, Pan C, Huang W (2014) Overexpression of sirt7 exhibits oncogenic property and serves as a prognostic factor in colorectal cancer. Clin Cancer Res 20(13):3434–3445. https://doi.org/10.1158/1078-0432.CCR-13-2952
Yu J, Wu Y, Yang P (2016) High glucose-induced oxidative stress represses sirtuin deacetylase expression and increases histone acetylation leading to neural tube defects. J Neurochem 137(3):371–383. https://doi.org/10.1111/jnc.13587
Zhang P, Tu B, Wang H, Cao Z, Tang M, Zhang C, Gu B, Li Z, Wang L, Yang Y, Zhao Y, Wang H, Luo J, Deng C-X, Gao B, Roeder RG, Zhu W-G (2014) Tumor suppressor p53 cooperates with SIRT6 to regulate gluconeogenesis by promoting FoxO1 nuclear exclusion. Proc Nat Acad Sci 111(29):10684. https://doi.org/10.1073/pnas.1411026111
Zhang J, Yin XJ, Xu CJ, Ning YX, Chen M, Zhang H, Chen SF, Yao LQ (2015) The histone deacetylase SIRT6 inhibits ovarian cancer cell proliferation via down-regulation of Notch 3 expression. Eur Rev Med Pharmacol Sci 19(5):818–824
Zhang N, Li Z, Mu W, Li L, Liang Y, Lu M, Wang Z, Qiu Y, Wang Z (2016) Calorie restriction-induced SIRT6 activation delays aging by suppressing NF-kappaB signaling. Cell Cycle 15(7):1009–1018. https://doi.org/10.1080/15384101.2016.1152427
Zhang X, Spiegelman NA, Nelson OD, **g H, Lin H (2017) SIRT6 regulates Ras-related protein R-Ras2 by lysine defatty-acylation. Elife 6:25158. https://doi.org/10.7554/eLife.25158
Zhao G, Wang H, Xu C, Wang P, Chen J, Wang P, Sun Z, Su Y, Wang Z, Han L, Tong T (2016) SIRT6 delays cellular senescence by promoting p27Kip1 ubiquitin-proteasome degradation. Aging (Albany NY) 8(10):2308–2323. https://doi.org/10.18632/aging.101038
Zhong L, D’Urso A, Toiber D, Sebastian C, Henry RE, Vadysirisack DD, Guimaraes A, Marinelli B, Wikstrom JD, Nir T, Clish CB, Vaitheesvaran B, Iliopoulos O, Kurland I, Dor Y, Weissleder R, Shirihai OS, Ellisen LW, Espinosa JM, Mostoslavsky R (2010) The histone deacetylase Sirt6 regulates glucose homeostasis via Hif1alpha. Cell 140(2):280–293. https://doi.org/10.1016/j.cell.2009.12.041
Zwaans BMM, Lombard DB (2014) Interplay between sirtuins, MYC and hypoxia-inducible factor in cancer-associated metabolic reprogramming. Dis Model Mech 7(9):1023–1032. https://doi.org/10.1242/dmm.016287
Author information
Authors and Affiliations
Corresponding authors
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2022 The Author(s), under exclusive license to Springer Nature Switzerland AG
About this chapter
Cite this chapter
Raghu, S., Prabhashankar, A.B., Shivanaiah, B., Tripathi, E., Sundaresan, N.R. (2022). Sirtuin 6 Is a Critical Epigenetic Regulator of Cancer. In: Kundu, T.K., Das, C. (eds) Metabolism and Epigenetic Regulation: Implications in Cancer. Subcellular Biochemistry, vol 100. Springer, Cham. https://doi.org/10.1007/978-3-031-07634-3_10
Download citation
DOI: https://doi.org/10.1007/978-3-031-07634-3_10
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-031-07633-6
Online ISBN: 978-3-031-07634-3
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)