Dramatic advances in cancer treatment will depend on identifying new targets for therapeutics. Here we propose as a candidate target a novel phosphoinositide signaling pathway that we have discovered. We have identified a pathway involving the phosphoinositide PtdIns(4)P and a new protein that binds to it which we have called PI4P-BP. We have shown that this pathway is required for normal Golgi architecture and function. Cancer cells often require autocrine, paracrine, or endocrine growth factor signaling for continued proliferation and survival. Since trafficking of growth factors and growth factor receptors requires intact Golgi function, interference with the Golgi is expected to interfere with cancer proliferation and survival. We have devised methods to inducibly interfere with the PtdIns(4)P/PI4P-BP pathway. We propose experiments to determine the effect of interference with the PtdIns(4)P/PI4P-BP pathway on growth factor signaling and thus whether it will be worthwhile to develop this novel therapeutic strategy further toward its clinical application.

Public Health Relevance

Dramatic advances in cancer treatment will depend on identifying new targets for therapeutics. We have identified a new signaling pathway that provides a new target for cancer therapies. The experiments that we propose will determine whether it will be worthwhile to further develop this novel therapeutic strategy for clinical application.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
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Drug Discovery and Molecular Pharmacology Study Section (DMP)
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Arya, Suresh
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University of California San Diego
Internal Medicine/Medicine
Schools of Medicine
La Jolla
United States
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Murray, Michael J; Ng, Michelle M; Fraval, Hamilton et al. (2012) Regulation of Drosophila mesoderm migration by phosphoinositides and the PH domain of the Rho GTP exchange factor Pebble. Dev Biol 372:17-27
Schmid, Michael C; Avraamides, Christie J; Dippold, Holly C et al. (2011) Receptor tyrosine kinases and TLR/IL1Rs unexpectedly activate myeloid cell PI3k?, a single convergent point promoting tumor inflammation and progression. Cancer Cell 19:715-27
Nhek, Sokha; Ngo, Mike; Yang, Xuemei et al. (2010) Regulation of oxysterol-binding protein Golgi localization through protein kinase D-mediated phosphorylation. Mol Biol Cell 21:2327-37
Dippold, Holly C; Ng, Michelle M; Farber-Katz, Suzette E et al. (2009) GOLPH3 bridges phosphatidylinositol-4- phosphate and actomyosin to stretch and shape the Golgi to promote budding. Cell 139:337-51
Bielas, Stephanie L; Silhavy, Jennifer L; Brancati, Francesco et al. (2009) Mutations in INPP5E, encoding inositol polyphosphate-5-phosphatase E, link phosphatidyl inositol signaling to the ciliopathies. Nat Genet 41:1032-6