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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Acknowledgments
This study was supported by research grants from National Natural Science Foundation of China (Nos. 81201532 and 81372195), Young Teacher Scientific Capability Promotion Project of Fudan University (No. 20520133490), Shanghai Pujiang Program (No. 13PJ1406000), Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning (No. 1410000157),Science and Technology Commission of Shanghai Municipality (No. 134119a5600) and Shanghai Municipal Commission of Health and Family Planning (XYQ2013109).
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Yan Sun and Weiwei He contributed equally to this work.
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Sun, Y., He, W., Luo, M. et al. SREBP1 regulates tumorigenesis and prognosis of pancreatic cancer through targeting lipid metabolism. Tumor Biol. 36, 4133–4141 (2015). https://doi.org/10.1007/s13277-015-3047-5
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DOI: https://doi.org/10.1007/s13277-015-3047-5