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International Journal Of Bilogical Sciences

.: Home > International Journal Of Bilogical Sciences > 2014 > Volume 10 Number 2 > Junqin Li1, Lihua Dong1, Dapeng Wei1, Xiaodong Wang2, Shuo Zhang1, Hua Li1

Fatty Acid Synthase Mediates the EpithelialMesenchymal Transition of Breast Cancer Cells

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

Date Deposited : 03 Feb 2016 11:10

Last Modified : 03 Feb 2016 11:10

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Volume 10, Number 2, - 2014 , ISSN 1449-2288

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