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.
Highlights
Ovarian cancer is the second most common gynecologic malignancy and the most common cause of gynecologic cancer related death worldwide [1]
Our work demonstrates that Fatty acid synthase (FASN) promotes the peritoneal dissemination of ovarian cancer cells, at least in part through the induction of Epithelial-mesenchymal Transition (EMT)
Peritoneal transcoelomic dissemination is the main common metastasis causing the greatest morbidity and mortality in women with this disease, and we determined the association of FASN expression with peritoneal metastasis
Summary
Ovarian cancer is the second most common gynecologic malignancy and the most common cause of gynecologic cancer related death worldwide [1]. 70% of women with ovarian cancer are diagnosed at an advanced stage with metastases, and only 45% of patients with advanced stage ovarian cancer survive 5 years after initial diagnosis [2]. The biological behavior of ovarian carcinoma is unique and different from the classic pattern of hematogenous metastasis found in most other cancers. Patients with ovarian carcinoma have locally advanced disease with contiguous extension to the outside of ovaries and abdominal peritoneum [3,4]. Transcoelomic metastasis, the most common route, is responsible for the greatest morbidity and mortality in women with this disease [5]. It is necessary to improve our understanding of how ovarian carcinoma spreads to the peritoneum
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