title: Programmed cell death 6 (PDCD6) inhibits angiogenesis through PI3K/mTOR/p70S6K pathway by interacting of VEGFR-2.
abstract: Programmed cell death 6 (PDCD6) was originally found as a pro-apoptotic protein, but its molecular mechanism is not well understood. In this study, we have attempted to investigate the effects of PDCD6 on the inhibition of angiogenesis-mediated cell growth as a novel anti-angiogenic protein. Purified recombinant human PDCD6 inhibited cell migration in a concentration-time-dependent manner. We also found that overexpressed PDCD6 suppressed vascular endothelial growth factor (VEGF)-induced proliferation, invasion, and capillary-like structure tube formation in vitro. PDCD6 suppressed phosphorylation of signaling regulators downstream from PI3K, including Akt, mammalian target of rapamycin (mTOR), glycogen synthase kinase-3β(GSK-3β), ribosomal protein S6 kinase (p70S6K), and also decreased cyclin D1 expression. We found binding PDCD6 to VEGFR-2, a key player in the PI3K/mTOR/P70S6K signaling pathway. Taken together, these data suggest that PDCD6 plays a significant role in modulating cellular angiogenesis.
authors: Research Institute, National Cancer Center, Ilsandong-gu, Goyang-si Gyeonggi-do, Republic of Korea. sbrho@ncc.re.kr
authors: Seung Bae
authors: SB
authors: Rho
authors: Yong Jung
authors: YJ
authors: Song
authors: Myong Cheol
authors: MC
authors: Lim
authors: Seung-Hoon
authors: SH
authors: Lee
authors: Boh-Ram
authors: BR
authors: Kim
authors: Sang-Yoon
authors: SY
authors: Park
mesh_terms: D020533:Angiogenesis Inhibitors / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D017930:Genes, Reporter; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism / Q000502:physiology; D006801:Humans; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000503:physiopathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism*; D015398:Signal Transduction; D018874:Spheroids, Cellular; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology / Q000502:physiology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
chemical_list: D020533:Angiogenesis Inhibitors; D051017:Apoptosis Regulatory Proteins; D002135:Calcium-Binding Proteins; D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D008156:Luciferases; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2; C097753:PDCD6 protein, human; C467484:VEGFA protein, human; C546842:MTOR protein, human; C000605506:GSK3B protein, human