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01-06-2015 | Research Article

SREBP1 regulates tumorigenesis and prognosis of pancreatic cancer through targeting lipid metabolism

Authors: Yan Sun, Weiwei He, Man Luo, Yuhong Zhou, Guilin Chang, Weiying Ren, Kefen Wu, Xi Li, Jiping Shen, Xiaoping Zhao, Yu Hu

Published in: Tumor Biology | Issue 6/2015

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.

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Title: SREBP1 regulates tumorigenesis and prognosis of pancreatic cancer through targeting lipid metabolism
Authors: Yan Sun
Weiwei He
Man Luo
Yuhong Zhou
Guilin Chang
Weiying Ren
Kefen Wu
Xi Li
Jiping Shen
Xiaoping Zhao
Yu Hu
Publication date: 01-06-2015
Publisher: Springer Netherlands
Published in: Tumor Biology / Issue 6/2015
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI: https://doi.org/10.1007/s13277-015-3047-5

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