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Int J Biochem Cell Biol. 2013 Mar;45(3):745-52. doi: 10.1016/j.biocel.2012.11.001. Epub 2012 Nov 10.

Statins, autophagy and cancer metastasis.

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  • 1Department of Orthopedics, the Third Affiliated Hospital of Kunming Medical University, Tumor Hospital of Yunnan Province, Kunming 650118, PR China.

Abstract

Statins inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. They are traditionally considered to be cholesterol-lowering agents, but in recent years more and more effects of statins have been revealed, including anti-inflammation, immunomodulation, neuroprotection, improvement of bone metabolism, and antitumour effects. In the past few years, extensive studies have shown that statins can induce autophagy in tumour cells as well as in some normal cells, and autophagy may be involved in the regulation of cancer metastasis. This review is focused on summarising and discussing the relationships among statins, autophagy and cancer metastasis. Studies showed that activation of the AMPK-TOR signalling pathway may be a major mechanism of statin-induced autophagy. Depleting cellular geranylgeranyl diphosphate activates AMPK and inactivates TOR, leading to autophagic responses. Autophagy, a strategy of self-adaption, is a double-edged sword in tumour metastasis. On one hand, autophagy contributes to anti-metastasis activity by, for example, restricting tumour necrosis and inflammatory cell infiltration of tumours and promoting the release of high-mobility group box protein 1 that triggers strong antitumour immune responses. On the other hand, it also exhibits a pro-metastasis activity. In summary, we propose a working hypothesis: statins induce autophagy in cancer cells, and this constitutes, at least in part, the basis for the anti-metastatic effect of statins. The idea that autophagy is responsible for statin-induced anti-metastasis effects is probably novel, and it extends the conventional view that interference of the post-translational modification of Rho GTPases by statins prevents tumour metastasis.

Copyright © 2012 Elsevier Ltd. All rights reserved.

PMID:
23147595
[PubMed - indexed for MEDLINE]
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