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KMID : 0613820140240050588
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Journal of Life Science
2014 Volume.24 No. 5 p.588 ~ p.593
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RalA-binding Protein 1 is an Important Regulator of Tumor Angiogenesis
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Lee Seung-Hyung
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Abstract
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Tumor angiogenesis is important in tumorigenesis and therapeutic interventions in cancer. To know inhibitor and effector of tumor angiogenesis in cancer, the specific gene of tumor and angiogenesis may develop the mechanisms of cancer suppression and therapy. Recently, we described the role of RalA-binding protein 1 (RLIP76) in tumor angiogenesis. Tumor vascular volumes were diminished, and vessels were fewer in number, shorter, and narrower in RLIP76 knockout mice than in wild-type mice. Moreover, angiogenesis in basement membrane matrix plugs was blunted in the knockout mice in the absence of tumor cells, with endothelial cells isolated from the lungs of these animals exhibiting defects in migration, proliferation, and cord formation in vitro. RLIP76 is expressed in most human tissues and is overexpressed in many tumor types. In addition, the protein regulates tumorigenesis and angiogenesis in vivo and in vitro. As the export of chemotherapy agents is a prominent cellular function of RLIP76, it is a major factor in mechanisms of drug resistance. Moreover, RLIP76 acts as a selective effector of the small GTPase, R-Ras, and regulates R-Ras signaling, leading to cell spreading and migration. Furthermore, in skin carcinogenesis, RLIP76 knockout mice are resistant, with tumors that form showing diminished angiogenesis. Thus, RLIP76 is required for efficient endothelial cell function and angiogenesis in solid tumors.
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KEYWORD
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Cancer, Endothelial cell, RalBP1/RLIP76, Tumor angiogenesis, Tumorigenesis
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