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Int. J. Mol. Sci. 2014, 15(7), 11539-11554; doi:10.3390/ijms150711539

Up-Regulated FASN Expression Promotes Transcoelomic Metastasis of Ovarian Cancer Cell through Epithelial-Mesenchymal Transition

1
Department of Gynecology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China
2
Department of Clinical Laboratory, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 30 April 2014 / Revised: 17 June 2014 / Accepted: 20 June 2014 / Published: 27 June 2014
(This article belongs to the Special Issue Advances in Molecular Oncology 2014)
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Abstract

Fatty acid synthase (FASN), responsible for the de novo synthesis of fatty acids, has been shown to act as an oncogene in various human cancers. However, the mechanisms by which FASN favors the progression of ovarian carcinoma remain unknown. In this study, we evaluated FASN expression in ovarian cancer and investigated how FASN regulates the aggressiveness of ovarian cancer cells. Our results show that increased FASN is associated with the peritoneal metastasis of ovarian cancers. Over-expression of FASN results in a significant increase of tumor burden in peritoneal dissemination, accompanied by augment in cellular colony formation and metastatic ability. Correspondingly, FASN knockdown using RNA interference in ovarian cancer cells inhibits the migration in vitro and experimental peritoneal dissemination in vivo. Mechanistic studies reveal that FASN promotes Epithelial-mesenchymal Transition (EMT) via a transcriptional regulation of E-cadherin and N-cadherin, which is also confirmed by luciferase promoter activity analysis. Taken together, our work demonstrates that FASN promotes the peritoneal dissemination of ovarian cancer cells, at least in part through the induction of EMT. These findings suggest that FASN plays a critical role in the peritoneal metastasis of ovarian cancer. Targeting de novo lipogenesis may have a therapeutic potential for advanced ovarian cancer. View Full-Text
Keywords: ovarian cancer; fatty acid synthase; tumorigenicity; EMT ovarian cancer; fatty acid synthase; tumorigenicity; EMT
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Jiang, L.; Wang, H.; Li, J.; Fang, X.; Pan, H.; Yuan, X.; Zhang, P. Up-Regulated FASN Expression Promotes Transcoelomic Metastasis of Ovarian Cancer Cell through Epithelial-Mesenchymal Transition. Int. J. Mol. Sci. 2014, 15, 11539-11554.

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