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Comment
. 2012 Dec 7;151(6):1155-6.
doi: 10.1016/j.cell.2012.11.020.

SIRT6 puts cancer metabolism in the driver's seat

Costas A Lyssiotis  1 , Lewis C Cantley
Affiliations
Comment

SIRT6 puts cancer metabolism in the driver's seat

Costas A Lyssiotis et al. Cell. .

Abstract

The rewiring of metabolism in cancer is thought to result from hyperactivation of signaling pathways that instruct cells to grow. Sebastian et al. show that loss of the tumor suppressor SIRT6 transforms cells by activating tumor metabolism. This occurs independently of mutations in canonical growth signaling pathways and reveals a tumorigenic role for cancer metabolism.

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Figures

Figure 1
Figure 1. Loss of SIRT6-Mediated Suppression of Cancer Metabolism Promotes Tumorigenesis
(A) The deacetylase SIRT6 acts as acorepressor of HIF-1α- and MYC-dependent cancer metabolism but does not globally repress HIF-1α or MYC transcription. (B) SIRT6 inhibits aerobic glycolysis, anabolic glutamine metabolism, and ribosome biogenesis. Together, activation of these metabolic pathways promotes tumorigenesis and tumor growth. Inhibition of aerobic glycolysis by knockdown of PDK1 using short hairpin RNA (shPDK1) or pharmacological inhibition with dichloroacetate (DCA) blocks the tumorigenic activity of SIRT6 loss.
See this image and copyright information in PMC

Comment on

  • The histone deacetylase SIRT6 is a tumor suppressor that controls cancer metabolism.
    Sebastián 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. Sebastián C, et al. Cell. 2012 Dec 7;151(6):1185-99. doi: 10.1016/j.cell.2012.10.047. Cell. 2012. PMID: 23217706 Free PMC article.

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