GRK3 is essential for metastatic cells and promotes prostate tumor progression

Wenliang Li; Nanping Ai; Suming WangNandita BhattacharyaVladimir VrbanacMichael CollinsSabina SignorettiYanhui HuFrederick M. BoyceKarsten GravdalOle J. HalvorsenHawa NalwogaLars A. AkslenEd HarlowRandolph S. Watnick

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GRK3 is essential for metastatic cells and promotes prostate tumor progression

机译：GRK3 is essential for metastatic cells and promotes prostate tumor progression

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The biochemical mechanisms that regulate the process of cancer metastasis are still poorly understood. Because kinases, and the signaling pathways they comprise, play key roles in regulation of many cellular processes, we used an unbiased RNAi in vitro screen and a focused cDNA in vivo screen against human kinases to identify those with previously undocumented roles in metastasis. We discovered that G-protein-coupled receptor kinase 3 (GRK3; or β-adrenergic receptor kinase 2) was not only necessary for survival and proliferation of metastatic cells, but also sufficient to promote primary prostate tumor growth and metastasis upon exogenous expression in poorly metastatic cells in mouse xenograft models. Mechanistically, we found that GRK3 stimulated angiogenesis, at least in part through down-regulation of thrombospondin-1 and plasminogen activator inhibitor type 2. Furthermore, GRK3 was found to be overexpressed in human prostate cancers, especially in metastatic tumors. Taken together, these data suggest that GRK3 plays an important role in prostate cancer progression and metastasis.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2014年第4期|1521-1526|共6页
作者
Wenliang Li; Nanping Ai; Suming WangNandita BhattacharyaVladimir VrbanacMichael CollinsSabina SignorettiYanhui HuFrederick M. BoyceKarsten GravdalOle J. HalvorsenHawa NalwogaLars A. AkslenEd HarlowRandolph S. Watnick;
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作者单位

Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030;

Vascular Biology Program, Department of Surgery, Children's Hospital Boston, Boston, MA 02115;

Center of Cancer Systems Biology, Tufts University School of Medicine, Boston, MA 02135Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Charlestown, MA 02129Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115Department of Neurology, Massachusetts General Hospital, Cambridge, MA 02139Centre for Cancer Biomarkers, Department of Clinical Medicine, University of Bergen, N-5020 Bergen, Norway;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
functional screens; essential kinases; ADRBK2; TSP-1; PAI-2;

GRK3 is essential for metastatic cells and promotes prostate tumor progression

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