Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Aug 28;25(17):3935.
doi: 10.3390/molecules25173935.

Fatty Acid Synthase: An Emerging Target in Cancer

Chee Wai Fhu  1 , Azhar Ali  1
Affiliations
Review

Fatty Acid Synthase: An Emerging Target in Cancer

Chee Wai Fhu et al. Molecules. .

Abstract

In recent years, lipid metabolism has garnered significant attention as it provides the necessary building blocks required to sustain tumor growth and serves as an alternative fuel source for ATP generation. Fatty acid synthase (FASN) functions as a central regulator of lipid metabolism and plays a critical role in the growth and survival of tumors with lipogenic phenotypes. Accumulating evidence has shown that it is capable of rewiring tumor cells for greater energy flexibility to attain their high energy requirements. This multi-enzyme protein is capable of modulating the function of subcellular organelles for optimal function under different conditions. Apart from lipid metabolism, FASN has functional roles in other cellular processes such as glycolysis and amino acid metabolism. These pivotal roles of FASN in lipid metabolism make it an attractive target in the clinic with several new inhibitors currently being tested in early clinical trials. This article aims to present the current evidence on the emergence of FASN as a target in human malignancies.

Keywords: cancer; fatty acid synthase; lipid metabolism.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Fatty acid synthase (FASN) structure. (A) Represents the linear sequence organization of FASN monomer. (B). Structural overview of FASN comprising two identical monomers, each including seven catalytic domains: beta-ketoacyl synthase (KS), acetyl/malonyl transacylase (AT/MT), beta-hydroxyacyl dehydratase (DH), enoyl reductase (ER), beta-ketoacyl reductase (KR), acyl carrier protein (ACP), and thioesterase (TE).
Figure 2
Figure 2
Molecular mechanisms of FASN in cancer. Expression and activity of FASN can be regulated by the epidermal growth factor receptor (EGFR) family members, EGFR and epidermal growth factor receptor 2 (HER2). FASN is shown to regulate lipid synthesis, signaling of major oncogenic pathways (including phosphatidylinositol-3′-kinase (PI3K/AKT) and extracellular regulated kinase 1/2 (ERK1/2)) and modulate cellular mechanisms (including autophagy, DNA repair and transcription of Lysosome Biogenesis genes). FASN overexpression promotes proliferation and increases the metastatic potential of tumor cells.
See this image and copyright information in PMC

References

    1. Hanahan D., Weinberg R.A. The Hallmarks of Cancer. Cell. 2000;100:57–70. doi: 10.1016/S0092-8674(00)81683-9. - DOI - PubMed
    1. Hanahan D., Weinberg R.A. Hallmarks of Cancer: The Next Generation. Cell. 2011;144:646–674. doi: 10.1016/j.cell.2011.02.013. - DOI - PubMed
    1. Warburg O. On the Origin of Cancer Cells. Science. 1956;123:309–314. doi: 10.1126/science.123.3191.309. - DOI - PubMed
    1. Ventura R., Mordec K., Waszczuk J., Wang Z., Lai J., Fridlib M., Buckley D., Kemble G., Heuer T.S. Inhibition of de novo Palmitate Synthesis by Fatty Acid Synthase Induces Apoptosis in Tumor Cells by Remodeling Cell Membranes, Inhibiting Signaling Pathways, and Reprogramming Gene Expression. EBioMedicine. 2015;2:808–824. doi: 10.1016/j.ebiom.2015.06.020. - DOI - PMC - PubMed
    1. Chirala S.S., Wakil S.J. Structure and function of animal fatty acid synthase. Lipids. 2004;39:1045–1053. doi: 10.1007/s11745-004-1329-9. - DOI - PubMed

MeSH terms