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Int J Biol Sci 2014; 10(2):171-180. doi:10.7150/ijbs.7357 This issue Cite

Research Paper

Fatty Acid Synthase Mediates the Epithelial-Mesenchymal Transition of Breast Cancer Cells

Junqin Li1, Lihua Dong1, Dapeng Wei1, Xiaodong Wang2, Shuo Zhang1, Hua Li1✉

1. Department of Basic and Forensic Medicine, Sichuan University, Sichuan Province, 610041, China.
2. West China Hospital, Sichuan University, Sichuan Province, 610041, China.

✉ Corresponding author: Hua Li, West China College of Basic and Forensic Medicine, Sichuan University, 17 People's South Road, Chengdu, Sichuan Province, 610041, China. E-mail address: lihua_scuedu.cn.

Citation:
Li J, Dong L, Wei D, Wang X, Zhang S, Li H. Fatty Acid Synthase Mediates the Epithelial-Mesenchymal Transition of Breast Cancer Cells. Int J Biol Sci 2014; 10(2):171-180. doi:10.7150/ijbs.7357. https://www.ijbs.com/v10p0171.htm
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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.

Keywords: EMT, FASN, L-FABP, VEGF, Breast cancer.

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APA
Li, J., Dong, L., Wei, D., Wang, X., Zhang, S., Li, H. (2014). Fatty Acid Synthase Mediates the Epithelial-Mesenchymal Transition of Breast Cancer Cells. International Journal of Biological Sciences, 10(2), 171-180. https://doi.org/10.7150/ijbs.7357.

ACS
Li, J.; Dong, L.; Wei, D.; Wang, X.; Zhang, S.; Li, H. Fatty Acid Synthase Mediates the Epithelial-Mesenchymal Transition of Breast Cancer Cells. Int. J. Biol. Sci. 2014, 10 (2), 171-180. DOI: 10.7150/ijbs.7357.

NLM
Li J, Dong L, Wei D, Wang X, Zhang S, Li H. Fatty Acid Synthase Mediates the Epithelial-Mesenchymal Transition of Breast Cancer Cells. Int J Biol Sci 2014; 10(2):171-180. doi:10.7150/ijbs.7357. https://www.ijbs.com/v10p0171.htm

CSE
Li J, Dong L, Wei D, Wang X, Zhang S, Li H. 2014. Fatty Acid Synthase Mediates the Epithelial-Mesenchymal Transition of Breast Cancer Cells. Int J Biol Sci. 10(2):171-180.

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