The acetyl-CoA carboxylase enzyme: a target for cancer therapy?

Abstract

As a rate-limiting enzyme, the acetyl-CoA carboxylase (ACC) is essential for fatty acid synthesis. Traditionally, the ACC has been a target of metabolic syndrome and obesity. Recent research has demonstrated that malignant tumors have a high energy flow, thus having a great ability to synthesize fatty acids. ACCs are occasionally found to be overexpressed in cancer cells, and using chemical or RNA interference to inhibit ACC can lead to cancer cell cycle arrest and apoptosis. This suggests that ACC and relative fatty acids may be critical for the survival of cancer cells. In this review, we summarize the role of ACC in tumor development. We also discuss the signaling pathways possibly affected by ACC, which may give insight into future research for cancer therapy.

Keywords:

• acetyl-CoA carboxylase
• cell cycle
• cell signaling
• fatty acids synthesis
• tumor metabolism

Acknowledgements

This review is supported by Shanghai Education Committee Scientific Project No.11YZ49. The authors are grateful for some advice given by Lin from Mayo Clinic.

Financial & competing interests’ disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• De novo fatty acid overproduction is often found in all malignant tumors, and seems to be associated with poor prognosis.

• However, whether the overproduction of fatty acids is essential for tumor metastasis or is just a side effect of the enzyme overexpression is yet to be elucidated.

• As de novo fatty acid synthesis is rare in normal tissues, medication target on fatty acid–related enzymes would be an attractive option.

• Aside from fatty acid synthesis, acetyl-coA carboxylase and its phosphorylation are also involved in some important signaling pathways like the AMP-dependent protein kinase pathway. More attention should been paid on this enzyme in future studies.

• Till now, acetyl-coA carboxylase and related signaling pathways are not very clear. As a lipogenesis-associated pathway, the AMP-dependent protein kinase pathway should be the major pathway that should be focused.

Notes