title: SREBP1 regulates tumorigenesis and prognosis of pancreatic cancer through targeting lipid metabolism.
abstract: Sterol regulatory element-binding protein 1 (SREBP1) is a known transcription factor of lipogenic genes, which plays important roles in regulating de novo lipogenesis. Accumulating evidences indicate SREBP1 is involved in tumorigenesis, yet its role in pancreatic cancer remains unclear. Here, we explored the expression characteristic and function of SREBP1 in pancreatic cancer. Analysis of 60 patients with pancreatic ducat cancer showed that SREBP1 level was significantly higher in pancreatic cancer than that in adjacent normal tissues. High expression of SREBP1 predicted poor prognosis in patients with pancreatic cancer. Multivariate analysis revealed that SREBP1 was an independent factor affecting overall survival. SREBP1 silencing resulted in proliferation inhibition and induction of apoptosis in pancreatic cancer cells. Mechanistically, lipogenic genes (acetyl-CoA carboxylase (ACC), fatty acid synthase (FASN), and stearoyl-CoA desaturase-1 (SCD1)) and de novo lipogenesis were promoted by SREBP1. Inhibition of lipogenic genes through specific inhibitors ablated SREBP1-mediated growth regulation. Furthermore, depletion of SREBP1 could suppress lipid metabolism and tumor growth in vivo. Our results indicate that SREBP1 had important role in tumor progression and appears to be a novel prognostic marker for pancreatic cancer.
authors.affiliation: Department of Geriatrics, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.forename: Weiwei
authors.initials: W
authors.lastname: He
authors.forename: Man
authors.initials: M
authors.lastname: Luo
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Zhou
authors.forename: Guilin
authors.initials: G
authors.lastname: Chang
authors.forename: Weiying
authors.initials: W
authors.lastname: Ren
authors.forename: Kefen
authors.initials: K
authors.lastname: Wu
authors.forename: Xi
authors.initials: X
authors.lastname: Li
authors.forename: Jiping
authors.initials: J
authors.lastname: Shen
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zhao
authors.forename: Yu
authors.initials: Y
authors.lastname: Hu
mesh_terms: D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D063646:Carcinogenesis / Q000235:genetics*; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics*; D050155:Lipogenesis / Q000235:genetics; D008297:Male; D051379:Mice; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D051780:Sterol Regulatory Element Binding Protein 1 / Q000096:biosynthesis* / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1