Related Experiment Video
Updated: Jul 14, 2026
Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer
Published on: March 17, 2016
Genome-wide changes accompanying knockdown of fatty acid synthase in breast cancer
Lynn M Knowles1, Jeffrey W Smith
1Cancer Research Center, Burnham Institute for Medical Research, La Jolla, CA 92037, USA. lknowles@burnham.org <lknowles@burnham.org>
Background:
The lipogenic enzyme fatty acid synthase (FAS) is up-regulated in a wide variety of cancers, and is considered a potential metabolic oncogene by virtue of its ability to enhance tumor cell survival. Inhibition of tumor FAS causes both cell cycle arrest and apoptosis, indicating FAS is a promising target for cancer treatment.
Results:
Here, we used gene expression profiling to conduct a global study of the cellular processes affected by siRNA mediated knockdown of FAS in MDA-MB-435 mammary carcinoma cells. The study identified 169 up-regulated genes (> or = 1.5 fold) and 110 down-regulated genes (< or = 0.67 fold) in response to knockdown of FAS. These genes regulate several aspects of tumor function, including metabolism, cell survival/proliferation, DNA replication/transcription, and protein degradation. Quantitative pathway analysis using Gene Set Enrichment Analysis software further revealed that the most pronounced effect of FAS knockdown was down-regulation in pathways that regulate lipid metabolism, glycolysis, the TCA cycle and oxidative phosphorylation. These changes were coupled with up-regulation in genes involved in cell cycle arrest and death receptor mediated apoptotic pathways.
Conclusion:
Together these findings reveal a wide network of pathways that are influenced in response to FAS knockdown and provide new insight into the role of this enzyme in tumor cell survival and proliferation.
Insights
Inhibiting fatty acid synthase (FAS) in cancer cells impacts numerous cellular processes, including metabolism and proliferation. This reveals FAS as a key target for developing novel cancer therapies.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Fatty acid synthase (FAS) is a lipogenic enzyme frequently upregulated in various cancers.
- FAS is recognized as a metabolic oncogene, promoting tumor cell survival.
- Inhibiting FAS induces cell cycle arrest and apoptosis, highlighting its therapeutic potential.
Purpose of the Study:
- To investigate the global cellular effects of fatty acid synthase (FAS) knockdown in mammary carcinoma cells.
- To identify genes and pathways regulated by FAS in cancer cells.
- To elucidate the role of FAS in tumor cell survival and proliferation.
Main Methods:
- Gene expression profiling using siRNA-mediated knockdown of FAS in MDA-MB-435 cells.
- Identification of differentially expressed genes (up-regulated and down-regulated).
- Quantitative pathway analysis using Gene Set Enrichment Analysis (GSEA).
Main Results:
- FAS knockdown led to 169 upregulated and 110 downregulated genes.
- Affected genes regulate metabolism, cell survival, proliferation, DNA replication, and protein degradation.
- Significant downregulation of lipid metabolism, glycolysis, TCA cycle, and oxidative phosphorylation pathways.
- Upregulation of genes involved in cell cycle arrest and apoptosis.
Conclusions:
- FAS knockdown influences a broad network of cellular pathways.
- These findings provide new insights into FAS's role in tumor cell survival and proliferation.
- FAS represents a promising therapeutic target for cancer treatment.