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

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• 作者：Dan Luo ; Huiwen Xiao ; Jiali Dong ; Yuan Li ; Guoxing Feng ; Ming Cui ; ^{cuiming0403@bjmu.edu.cn} ; Saijun Fan ; ^{fansaijun@irm-cams.ac.cn}
• 关键词：B7-H3 ; SREBP1 ; FASN ; Abnormal lipid metabolism ; Lung cancer
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2017
• 出版时间：22 January 2017
• 年：2017
• 卷：482
• 期：4
• 页码：1246-1251
• 全文大小：1616 K
• 卷排序：482

文摘

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.