title: 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: 1. Department of Basic and Forensic Medicine, Sichuan University, Sichuan Province, 610041, China.
authors: Junqin
authors: J
authors: Li
authors: 1. Department of Basic and Forensic Medicine, Sichuan University, Sichuan Province, 610041, China.
authors: Lihua
authors: L
authors: Dong
authors: 1. Department of Basic and Forensic Medicine, Sichuan University, Sichuan Province, 610041, China.
authors: Dapeng
authors: D
authors: Wei
authors: 2. West China Hospital, Sichuan University, Sichuan Province, 610041, China.
authors: Xiaodong
authors: X
authors: Wang
authors: 1. Department of Basic and Forensic Medicine, Sichuan University, Sichuan Province, 610041, China.
authors: Shuo
authors: S
authors: Zhang
authors: 1. Department of Basic and Forensic Medicine, Sichuan University, Sichuan Province, 610041, China.
authors: Hua
authors: H
authors: Li
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D002465:Cell Movement / Q000187:drug effects; D002569:Cerulenin / Q000494:pharmacology; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D064429:Fatty Acid Synthases / Q000502:physiology*; D054872:Fatty Acid Synthesis Inhibitors / Q000494:pharmacology; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D048671:MAP Kinase Kinase 5 / Q000235:genetics / Q000378:metabolism; D061986:MCF-7 Cells; D051379:Mice; D008819:Mice, Nude; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D054872:Fatty Acid Synthesis Inhibitors; D050556:Fatty Acid-Binding Proteins; D042461:Vascular Endothelial Growth Factor A; D002569:Cerulenin; D064429:Fatty Acid Synthases; D048671:MAP Kinase Kinase 5; C482563:MAP2K5 protein, human
keywords: Breast cancer.; EMT; FASN; L-FABP; VEGF