Up-regulation of fatty acid synthase induced by EGFR/ERK activation promotes tumor growth in pancreatic cancer
Up-regulation of fatty acid synthase induced by EGFR/ERK activation promotes tumor growth in pancreatic cancer
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DOI：
10.1016/j.bbrc.2015.05.108
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发表时间：
2015-08-07
影响因子：
3.1
通讯作者：
Li, Lin
中科院分区：
文献类型：
--
作者：
Bian, Yong;Yu, Yun;Li, Lin
脂质代谢在许多人类疾病中失调，包括动脉粥样硬化、2 型糖尿病和癌症。脂肪酸合酶 (FASN) 是一种参与脂质从头生物合成的关键脂肪生成酶，在多种类型的人类癌症中显着上调，并与肿瘤进展相关。然而，可用于了解胰腺导管腺癌 (PDAC) 中过度表达 FASN 的潜在生物学功能和临床意义的数据有限。在这里，与组织微阵列中的正常胰腺相比，在 PDAC 组织中更频繁地观察到 FASN 上调。 Kaplan-Meier生存分析显示FASN的高表达水平导致PDAC患者的预后明显较差。内源 FASN 的敲低或抑制会降低 HPAC 和 AsPC-1 细胞的细胞增殖并增加细胞凋亡。此外，我们通过进行 siRNA 测定和使用特定的药理学抑制剂，证明了 EGFR/ERK 信号传导导致了 PDAC 中 FASN 表达的升高。总的来说，我们的结果表明 FASN 在肿瘤生长中发挥重要作用，并且 EGFR/ERK 通路负责 PDAC 中 FASN 表达的上调。 (C) 2015 Elsevier Inc. 保留所有权利。
Lipid metabolism is dysregulated in many human diseases including atherosclerosis, type 2 diabetes and cancers. Fatty acid synthase (FASN), a key lipogenic enzyme involved in de novo lipid biosynthesis, is significantly upregulated in multiple types of human cancers and associates with tumor progression. However, limited data is available to understand underlying biological functions and clinical significance of overexpressed FASN in pancreatic ductal adenocarcinoma (PDAC). Here, upregulated FASN was more frequently observed in PDAC tissues compared with normal pancreas in a tissue microarray. Kaplan-Meier survival analysis revealed that high expression level of FASN resulted in a significantly poor prognosis of PDAC patients. Knockdown or inhibition of endogenous FASN decreased cell proliferation and increased cell apoptosis in HPAC and AsPC-1 cells. Furthermore, we demonstrated that EGFR/ERK signaling accounts for elevated FASN expression in PDAC as ascertained by performing siRNA assays and using specific pharmacological inhibitors. Collectively, our results indicate that FASN exhibits important roles in tumor growth and EGFR/ERK pathway is responsible for upregulated expression of FASN in PDAC. (C) 2015 Elsevier Inc. All rights reserved.