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. 2011 Jun;2(6):648-62.
doi: 10.1177/1947601911417862.

The dual role of sirtuins in cancer

Laia Bosch-Presegué  1 , Alejandro Vaquero
Affiliations

The dual role of sirtuins in cancer

Laia Bosch-Presegué et al. Genes Cancer. 2011 Jun.

Abstract

Among the greatest challenges facing organisms is that of detecting and effectively responding to life-threatening environmental changes that are intimately associated with metabolic fluctuations and certain forms of stress. These conditions have been linked to the onset of many human pathologies, including cancer. Over the past decade, members of the Sir2 family, or sirtuins, have been described as major players in sensing and coordinating stress response. Evidence has imputed mammalian sirtuins in carcinogenesis, although the mechanisms involved seem to be more diverse and complex than previously anticipated. Some sirtuins, such as SirT2 and SirT6, seem to work as tumor suppressors, but others, such as SirT1, are apparently bifunctional: operating as both tumor suppressors and oncogenic factors depending on the context and the study conditions. The mechanisms underlying these apparently contradictory activities are not well understood, although recent findings suggest that they might actually be two sides of the same coin. In this review, the authors summarize current knowledge on the functional implications of sirtuins in cancer and discuss possible explanations for their functional duality.

Keywords: DNA damage; DNA repair; SirT1-7; cancer; deacetylation; genome stability; heterochromatin; sirtuins.

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Conflict of interest statement

The authors declare that there are no potential conflicts of interest with respect to the authorship and/or publication of this article.

Figures

Figure 1.
Figure 1.
Sirtuins and DNA repair. Sirtuins are involved in DNA damage signaling and different DNA repair pathways (in red). The factors and pathways, through which they exert this function, are indicated. The link between SirT6 and BER has been established, although whether it is direct or not is still under discussion.
Figure 2.
Figure 2.
Sirtuins and cell survival. Under different forms of stress, sirtuins control cell fate through, among other mechanisms, modulation of apoptosis. The decision process before a particular situation is based as a result on a complex net of interactions and targets established by different sirtuins. The main described mediators and pathways of this sirtuin-dependent signaling are indicated.
Figure 3.
Figure 3.
SirT1 as a tumor suppressor or/and tumor promoter. The evidence reported supports both an oncogenic and a tumor suppressor role for SirT1. Here, we indicate the different functions described for SirT1 that support one role or the other.
Figure 4.
Figure 4.
Model for SirT1 apparent duality in cancer. (A) Under stress conditions, SirT1 promotes cell cycle arrest, DNA repair, and, ultimately, cell survival. In chronic stress conditions or under certain massive levels of DNA damage, SirT1 induces senescence and apoptosis. (B) Under chronic stress and loss of tumor suppressors or checkpoints, SirT1 promotes tumor formation and cancer. A feedback between tumor progression and SirT1 levels is established, resulting in reinforced dedifferentiation, cell growth, and cell survival.
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