SREBP1 regulates tumorigenesis and prognosis of pancreatic cancer through targeting lipid metabolism
SREBP1 regulates tumorigenesis and prognosis of pancreatic cancer through targeting lipid metabolism
复制标题
SREBP1通过靶向脂质代谢调节胰腺癌的肿瘤发生和预后。
DOI：
10.1007/s13277-015-3047-5
复制
发表时间：
2015-06-01
期刊：
影响因子：
--
通讯作者：
Hu, Yu
中科院分区：
文献类型：
--
作者：
Sun, Yan;He, Weiwei;Hu, Yu
固醇调节元件结合蛋白1(SREBP1)是已知的成脂基因转录因子，在调节新生脂肪生成中发挥重要作用。越来越多的证据表明，SREBP1参与了肿瘤的发生，但其在胰腺癌中的作用尚不清楚。本研究旨在探讨SREBP1在胰腺癌中的表达特点和功能。对60例胰腺癌患者的分析表明，胰腺癌组织中SREBP1水平明显高于癌旁正常组织。SREBP1高表达预示胰腺癌患者预后不良。多因素分析显示，SREBP1是影响总生存率的独立因素。SREBP1沉默可抑制胰腺癌细胞增殖，诱导细胞凋亡。从机制上讲，SREBP1促进了脂肪生成基因(乙酰辅酶A羧基酶(ACC)、脂肪酸合成酶(FASN)和硬脂酰辅酶A脱饱和酶-1(SCD1))和从头脂肪生成。通过特定的抑制物抑制生脂基因可抑制SREBP1介导的生长调节。此外，SREBP1的缺失可以抑制体内的脂代谢和肿瘤生长。我们的结果表明，SREBP1在肿瘤进展中起着重要作用，有望成为胰腺癌新的预后标志物。
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.