Inositol phosphate recycling regulates glycolytic and lipid metabolism that drives cancer aggressiveness.

Abstract

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.

• Authors: 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
• Journal: ACS chemical biology (ACS Chem Biol) Vol. 9 Issue 6 Pg. 1340-50 (Jun 20 2014) ISSN: 1554-8937 [Electronic] United States
• PMID: 24738946 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Inositol Phosphates
• RNA, Small Interfering
• Phosphoric Monoester Hydrolases
• inositol-1,4-bisphosphate 1-phosphatase

Topics

• Animals
• Apoptosis (drug effects)
• Blotting, Western
• Carcinoma, Papillary (drug therapy, metabolism, pathology)
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Cystadenocarcinoma, Serous (drug therapy, metabolism, pathology)
• Female
• Glycolysis (drug effects)
• Humans
• Inositol Phosphates (pharmacology)
• Lipid Metabolism (drug effects)
• Metabolome (drug effects)
• Mice
• Mice, SCID
• Neoplasms (drug therapy, metabolism, pathology)
• Ovarian Neoplasms (drug therapy, metabolism, pathology)
• Phosphoric Monoester Hydrolases (antagonists & inhibitors, genetics, metabolism)
• RNA, Small Interfering (genetics)
• Signal Transduction (drug effects)
• Tumor Cells, Cultured