Int J Biol Sci 2014; 10(2):171-180. doi:10.7150/ijbs.7357
Fatty Acid Synthase Mediates the Epithelial-Mesenchymal Transition of Breast Cancer Cells
1. Department of Basic and Forensic Medicine, Sichuan University, Sichuan Province, 610041, China.
2. West China Hospital, Sichuan University, Sichuan Province, 610041, China.
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.
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. Available from http://www.ijbs.com/v10p0171.htm