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Repression of endometrial tumor growth by targeting SREBP1 and lipogenesis
Journal article   Open access   Peer reviewed

Repression of endometrial tumor growth by targeting SREBP1 and lipogenesis

Weihua Li, Yanhong Tai, Jie Zhou, Weiting Gu, Zhaofang Bai, Tao Zhou, Zhijiu Zhong, Peter A. McCue, Nianli Sang, Jun-Yuan Ji, …
Cell cycle (Georgetown, Tex.), v 11(12), pp 2348-2358
15 Jun 2012
PMID: 22672904
url
https://doi.org/10.4161/cc.20811View
Published, Version of Record (VoR)Maybe Open Access (Publisher Bronze) Open

Abstract

cell death cell growth endometrial cancer lipogenesis Report SREBP1
The aberrantly increased lipogenesis is a universal metabolic feature of proliferating tumor cells. Although most normal cells acquire the bulk of their fatty acids from circulation, tumor cells synthesize more than 90% of required lipids de novo. The sterol regulatory element-binding protein 1 (SREBP1), encoded by SREBF1 gene, is a master regulator of lipogenic gene expression. SREBP1 and its target genes are overexpressed in a variety of cancers; however, the role of SREBP1 in endometrial cancer is largely unknown. We have screened a cohort of endometrial cancer (EC) specimen for their lipogenic gene expression and observed a significant increase of SREBP1 target gene expression in cancer cells compared with normal endometrium. By using immunohistochemical staining, we confirmed SREBP1 protein overexpression and demonstrated increased nuclear distribution of SREBP1 in EC. In addition, we found that knockdown of SREBP1 expression in EC cells suppressed cell growth, reduced colonigenic capacity and slowed tumor growth in vivo. Furthermore, we observed that knockdown of SREBP1 induced significant cell death in cultured EC cells. Taken together, our results show that SREBP1 is essential for EC cell growth both in vitro and in vivo, suggesting that SREBP1 activity may be a novel therapeutic target for endometrial cancers.

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Cell Biology
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