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Targeting a Novel Phosphoinositide Signaling Pathway for Cancer Therapy

针对癌症治疗的新型磷酸肌醇信号通路

基本信息

批准号：
7633803
负责人：
SETH J FIELD
金额：
$ 24.89万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-06-04 至 2011-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7633803
关键词：
Acute American Apoptotic Architecture Cancerous Cell Death Cell Proliferation Cell Survival Cell membrane Cells Data Development Endocrine Endoplasmic Reticulum Engineering Equipment and Supplies Family Funding Golgi Apparatus Golgi Targeting Growth Factor Growth Factor Receptors IGF-1 Signaling Pathway Malignant Neoplasms Methods Normal Cell Occupations Pathway interactions Pharmaceutical Preparations Phosphatidylinositols Platelet-Derived Growth Factor Play Protein Binding Recovery Role Signal Pathway Signal Transduction System Testing Therapeutic Vesicle autocrine cancer cell cancer therapy cell growth cell transformation chemotherapeutic agent clinical application endoplasmic reticulum stress new therapeutic target novel novel therapeutics paracrine protein misfolding research study tool trafficking treatment strategy

项目摘要

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.

癌症治疗的巨大进展将取决于确定新的治疗靶点。在这里，我们建议将我们发现的新型磷酸肌醇信号通路作为候选靶点。我们已经确定了一条涉及磷酸肌醇 PtdIns(4)P 的途径以及与其结合的新蛋白质，我们称之为PI4P-BP。我们已经证明，这条通路是正常高尔基体结构和功能所必需的。癌细胞通常需要自分泌、旁分泌或内分泌生长因子信号传导才能持续增殖和存活。由于生长因子和生长因子受体的运输需要完整的高尔基体功能，因此干扰高尔基体预计会干扰癌症的增殖和存活。我们设计了诱导干扰 PtdIns(4)P/PI4P-BP 途径的方法。我们提出实验来确定干扰 PtdIns(4)P/PI4P-BP 通路对生长因子信号传导的影响，从而确定是否值得进一步开发这种新型治疗策略以实现其临床应用。