| 3-phosphoinositide-dependent protein kinase-1 regulates proliferation and survival of cancer cells with an activated mitogen-activated protein kinase pathway. | |
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MedLine Citation:
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PMID: 20197379 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Engagement of cell surface receptor tyrosine kinases by insulin and growth factors activates phosphatidylinositol 3-kinase (PI3K) and generates the second messenger, phosphatidylinositol 3,4,5-trisphosphate. This second messenger leads to the recruitment of 3-phosphoinositide-dependent protein kinase-1 (PDK1) to the proximal side of the plasma membrane, which results in the activation of AKT kinase. In addition, PDK1 can phosphorylate numerous other kinases, including p90RSK, a kinase downstream of mitogen-activated protein kinase (MAPK) that is important for cell proliferation and survival. Previous studies have shown that the loss of PDK1 sensitizes tumor cells to chemotherapeutic agents and radiation but have not focused on delineating the contribution of PDK1 to pathway-specific mutations associated with various cancers other than the PI3K/AKT pathway. In this study, we show that the reduction of PDK1 by RNAi in melanoma and colon cancer cell lines activated in the MAPK pathway results in significant cell growth inhibition and apoptosis. Furthermore, PDK1 reduction in tumor cells resulted in impaired PAK kinase signaling, altered actin polymerization, and reduced cell migration. These studies show that PDK1 plays a pivotal role in MAPK and PI3K signaling in tumor cells. |
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Authors:
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Zhuomei Lu; Mary Ann Cox-Hipkin; William T Windsor; Anita Boyapati |
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Publication Detail:
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Type: Journal Article Date: 2010-03-02 |
Journal Detail:
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Title: Molecular cancer research : MCR Volume: 8 ISSN: 1557-3125 ISO Abbreviation: Mol. Cancer Res. Publication Date: 2010 Mar |
Date Detail:
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Created Date: 2010-03-18 Completed Date: 2010-07-12 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101150042 Medline TA: Mol Cancer Res Country: United States |
Other Details:
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Languages: eng Pagination: 421-32 Citation Subset: IM |
Affiliation:
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Schering-Plough Research Institute, Kenilworth, NJ 07033, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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1-Phosphatidylinositol 3-Kinase
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genetics,
metabolism* Apoptosis / genetics Carcinoma / enzymology, genetics Cell Line, Tumor Cell Proliferation* Cell Survival / genetics Colonic Neoplasms / enzymology, genetics Down-Regulation / genetics Enzyme Activation / genetics Gene Expression Regulation, Enzymologic / genetics Gene Expression Regulation, Neoplastic / genetics Humans MAP Kinase Signaling System / genetics Melanoma / enzymology, genetics Neoplasms / enzymology*, genetics Phosphatidylinositol Phosphates / metabolism Protein-Serine-Threonine Kinases / genetics, metabolism* RNA Interference / physiology |
| Chemical | |
Reg. No./Substance:
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0/Phosphatidylinositol Phosphates; 0/phosphatidylinositol 3,4,5-triphosphate; EC 2.7.1.-/3-phosphoinositide-dependent protein kinase; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase; EC 2.7.11.1/Protein-Serine-Threonine Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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