Inositol Phosphate Recycling Regulates Glycolytic and Lipid Metabolism That Drives Cancer Aggressiveness
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- 作者：Daniel I. Benjamin ; Sharon M. Louie ; Melinda M. Mulvihill ; Rebecca A. Kohnz ; Daniel S. Li ; Lauryn G. Chan ; Antonio Sorrentino ; Sourav Bandyopadhyay ; Alyssa Cozzo ; Anayo Ohiri ; Andrei Goga ; Shu-Wing Ng ; Daniel K. Nomura
- 刊名：ACS Chemical Biology
- 出版年：2014
- 出版时间：June 20, 2014
- 年：2014
- 卷：9
- 期：6
- 页码：1340-1350
- 全文大小：720K
- 年卷期：v.9,no.6(June 20, 2014)
- ISSN：1554-8937
文摘
Cancer cells possess fundamentally altered metabolism that supports their pathogenic features, which includes a heightened reliance on aerobic glycolysis to provide precursors for synthesis of biomass. We show here that inositol polyphosphate phosphatase 1 (INPP1) is highly expressed in aggressive human cancer cells and primary high-grade human tumors. Inactivation of INPP1 leads to a reduction in glycolytic intermediates that feed into the synthesis of the oncogenic signaling lipid lysophosphatidic acid (LPA), which in turn impairs LPA signaling and further attenuates glycolytic metabolism in a feed-forward mechanism to impair cancer cell motility, invasiveness, and tumorigenicity. Taken together these findings reveal a novel mode of glycolytic control in cancer cells that can serve to promote key oncogenic lipid signaling pathways that drive cancer pathogenicity.