Englerin A Stimulates PKC¦È to Inhibit Insulin Signaling and to Simultaneously Activate HSF1: Pharmacologically Induced Synthetic Lethality

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• 作者：Carole Sourbier¹ ; Bradley T. Scroggins¹ ; Ranjala Ratnayake³ ; Thomas L. Prince¹ ; Sunmin Lee² ; Min-Jung Lee² ; Peter Literati Nagy⁴ ; Young H. Lee¹ ; Jane B. Trepel² ; John A. Beutler³ ; W. Marston Linehan¹ ; Len Neckers¹ ; ^{neckersl@mail.nih.gov}
• 刊名：Cancer Cell
• 出版年：2013
• 出版时间：11 February, 2013
• 年：2013
• 卷：23
• 期：2
• 页码：228-237
• 全文大小：1006 K

文摘

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Summary

The natural product englerin A (EA) binds to and activates protein kinase C-¦È (PKC¦È). EA-dependent activation of PKC¦È induces an insulin-resistant phenotype, limiting the access of tumor cells to glucose. At the same time, EA causes PKC¦È-mediated phosphorylation and activation of the transcription factor heat shock factor 1, an inducer of glucose dependence. By promoting glucose addiction, while simultaneously starving cells of glucose, EA proves to be synthetically lethal to highly glycolytic tumors.