Statins, autophagy and cancer metastasis.

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.

• Authors: Jing Zhang, Zuozhang Yang, Lin Xie, Lei Xu, Da Xu, Xuefeng Liu
• Journal: The international journal of biochemistry & cell biology (Int J Biochem Cell Biol) Vol. 45 Issue 3 Pg. 745-52 (Mar 2013) ISSN: 1878-5875 [Electronic] Netherlands
• PMID: 23147595 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Protein Kinases
• TOR Serine-Threonine Kinases
• AMP-Activated Protein Kinase Kinases
• rho GTP-Binding Proteins

Topics

• AMP-Activated Protein Kinase Kinases
• Antineoplastic Agents (administration & dosage, metabolism)
• Autophagy (drug effects)
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (administration & dosage, metabolism)
• Neoplasm Metastasis (drug therapy, pathology)
• Neoplasms (drug therapy, metabolism, pathology)
• Protein Kinases (metabolism)
• Protein Processing, Post-Translational (drug effects)
• Signal Transduction (drug effects)
• TOR Serine-Threonine Kinases (metabolism)
• rho GTP-Binding Proteins (metabolism)