B7-H3 regulates lipid metabolism of lung cancer through SREBP1-mediated expression of FASN

被引：63

作者：

Luo, Dan

Xiao, Huiwen

Dong, Jiali

Li, Yuan

Feng, Guoxing

Cui, Ming ^{[1
]}

Fan, Saijun ^{[1
]}

机构：

[1] Chinese Acad Med Sci, Inst Radiat Med, Tianjin Key Lab Radiat Med & Mol Nucl Med, 238 Baidi Rd, Tianjin 300192, Peoples R China

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2017年 / 482卷 / 04期

基金：

中国国家自然科学基金;

关键词：

B7-H3; SREBP1; FASN; Abnormal lipid metabolism; Lung cancer; ELEMENT-BINDING PROTEINS; FATTY-ACID SYNTHASE; CELLS;

D O I：

10.1016/j.bbrc.2016.12.021

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

B7-H3 is a glycoprotein overexpressed in cancer, but its functional contribution in this setting remains poorly understood. In the present study, we identified that the overexpression of B7-H3 in lung cancer resulted in aberrant lipid metabolism via SREBP-1/FASN signaling pathway. Immunohistochemical analysis of tissue microarrays revealed that approximately 80.4% (37/46) of lung cancer tissues were positive for B7-H3 accompanying poor prognosis. Notably, Oil red O staining and total triglyceride assay exhibited that down-regulation of B7-H3 decreased lipid synthesis in lung cancer A549 and H446 cell lines. Mechanistic investigations showed that B7-H3 modulated the expression of FASN, a fatty acid synthase, specifically. Furthermore, deletion of B7-H3 down-regulated the mRNA and protein levels of SREBP-1, a transcription factor governing the expression of FASN. Finally, correlation analysis between expression levels of B7-H3 and FASN exhibited a positive correlation in clinical lung cancer tissues. Overall, we conclude that B7-H3 hijacks SREBP-1/FASN signaling mediating abnormal lipid metabolism in lung cancer. Our finding provides new insights into the function and mechanism of B7-H3 in the development of lung cancer. (C) 2016 Elsevier Inc. All rights reserved.

引用

页码：1246 / 1251

页数：6

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