Fatty acid synthase mediates the epithelial-mesenchymal transition of breast cancer cells.

Abstract

This study aimed to investigate the role of fatty acid synthase (FASN) in the epithelial-mesenchymal transition (EMT) of breast cancer cells. MCF-7 cells and MCF-7 cells overexpressing mitogen-activated protein kinase 5 (MCF-7-MEK5) were used in this study. MCF-7-MEK5 cells showed stable EMT characterized by increased vimentin and decreased E-cadherin expression. An In vivo animal model was established using the orthotopic injection of MCF-7 or MCF-7-MEK5 cells. Real-time quantitative PCR and western blotting were used to detect the expression levels of FASN and its downstream proteins liver fatty acid-binding protein (L-FABP) and VEGF/VEGFR-2 in both in vitro and in vivo models (nude mouse tumor tissues). In MCF-7-MEK5 cells, significantly increased expression of FASN was associated with increased levels of L-FABP and VEGF/VEGFR-2. Cerulenin inhibited MCF-7-MEK5 cell migration and EMT, and reduced FASN expression and down-stream proteins L-FABP, VEGF, and VEGFR-2. MCF-7-MEK5 cells showed higher sensitivity to Cerulenin than MCF-7 cells. Immunofluorescence revealed an increase of co-localization of FASN with VEGF on the cell membrane and with L-FABP within MCF-7-MEK5 cells. Immunohistochemistry further showed that increased percentage of FASN-positive cells in the tumor tissue was associated with increased percentages of L-FABP- and VEGF-positive cells and the Cerulenin treatment could reverse the effect. Altogether, our results suggest that FASN is essential to EMT possibly through regulating L-FABP, VEGF and VEGFR-2. This study provides a theoretical basis and potential strategy for effective suppression of malignant cells with EMT.

• Authors: Junqin Li, Lihua Dong, Dapeng Wei, Xiaodong Wang, Shuo Zhang, Hua Li
• Journal: International journal of biological sciences (Int J Biol Sci) Vol. 10 Issue 2 Pg. 171-80 ( 2014) ISSN: 1449-2288 [Electronic] Australia
• PMID: 24520215 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Fatty Acid Synthesis Inhibitors
• Fatty Acid-Binding Proteins
• Vascular Endothelial Growth Factor A
• Cerulenin
• Fatty Acid Synthases
• MAP Kinase Kinase 5
• MAP2K5 protein, human

Topics

• Animals
• Breast Neoplasms (pathology)
• Cell Movement (drug effects)
• Cerulenin (pharmacology)
• Epithelial-Mesenchymal Transition (physiology)
• Fatty Acid Synthases (physiology)
• Fatty Acid Synthesis Inhibitors (pharmacology)
• Fatty Acid-Binding Proteins (metabolism)
• Female
• Gene Expression (drug effects)
• Humans
• MAP Kinase Kinase 5 (genetics, metabolism)
• MCF-7 Cells
• Mice
• Mice, Nude
• Vascular Endothelial Growth Factor A (metabolism)