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

International Journal of Molecular Sciences

Xiangliang Yuan¹  Li Jiang²  Jiarui Li²  Xuhong Fang²  Hong Pan²  Ping Zhang²  Hong Wang² 

[1] Department of Clinical Laboratory, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China;Department of Gynecology, Xin Hua Hospital Affiliated to Shanghai Jiao TongUniversity School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China;

关键词: ovarian cancer;    fatty acid synthase;    tumorigenicity;    EMT;   

DOI  :  10.3390/ijms150711539

来源: DOAJ

【 摘 要 】

Fatty acid synthase (FASN), responsible for the de novo synthesis offatty acids, has been shown to act as an oncogene in various humancancers. However, the mechanisms by which FASN favors the progression ofovarian carcinoma remain unknown. In this study, we evaluated FASNexpression in ovarian cancer and investigated how FASN regulates theaggressiveness of ovarian cancer cells. Our results show that increasedFASN is associated with the peritoneal metastasis of ovarian cancers.Over-expression of FASN results in a significant increase of tumorburden in peritoneal dissemination, accompanied by augment in cellularcolony formation and metastatic ability. Correspondingly, FASN knockdownusing RNA interference in ovarian cancer cells inhibits the migrationin vitro and experimental peritoneal dissemination in vivo. Mechanisticstudies reveal that FASN promotes Epithelial-mesenchymal Transition(EMT) via a transcriptional regulation ofE-cadherin and N-cadherin,which is also confirmed by luciferase promoter activity analysis. Takentogether, our work demonstrates that FASN promotes the peritonealdissemination of ovarian cancer cells, at least in part through theinduction of EMT.These findings suggest that FASN plays a criticalrole in the peritoneal metastasis of ovarian cancer. Targeting de novolipogenesis may have a therapeutic potential for advanced ovariancancer.

【 授权许可】

Unknown