Sterol regulatory element-binding protein 1 is required for ovarian tumor growth

Abstract

Re-programming of lipogenic signaling is one of the most significant alterations of tumor cell pathology. Consistent with a large demand for lipids, tumor cells express high levels of lipogenic enzymes, most of which are transcriptional targets of sterol regulatory element-binding protein 1 (SREBP1). However, the expression levels and the function of SREBP1 in ovarian cancer are largely unknown. Our study aimed to assess the oncogenic potential of SREBP1 in ovarian cancer. In this study, we showed that the SREBP1 protein expression was significantly higher in human ovarian cancer compared to benign and borderline ovarian tumors by immunohistochemical staining. Knockdown of SREBP1 by small hairpin RNA (shRNA) in ovarian cancer cells retarded cell growth, migration and invasion and enhanced cell apoptosis without significant effects on cell cycle distribution. In a xenograft SCID mouse model, SREBP1 silencing inhibited tumor growth in vivo and reduced the expression of SREBP1 downstream lipogenic genes at both the protein and mRNA levels. Taken together, the results from this study demonstrate a crucial role of SREBP1 in ovarian cancer growth, which establish SREBP1 as a novel therapeutic target for antitumor therapy.