title: Vascular RhoJ is an effective and selective target for tumor angiogenesis and vascular disruption.
abstract: Current antiangiogenic therapy is limited by its cytostatic nature and systemic side effects. To address these limitations, we have unveiled the role of RhoJ, an endothelial-enriched Rho GTPase, during tumor progression. RhoJ blockade provides a double assault on tumor vessels by both inhibiting tumor angiogenesis and disrupting the preformed tumor vessels through the activation of the RhoA-ROCK (Rho kinase) signaling pathway in tumor endothelial cells, consequently resulting in a functional failure of tumor vasculatures. Moreover, enhanced anticancer effects were observed when RhoJ blockade was employed in concert with a cytotoxic chemotherapeutic agent, angiogenesis-inhibiting agent, or vascular-disrupting agent. These results identify RhoJ blockade as a selective and effective therapeutic strategy for targeting tumor vasculature with minimal side effects.
authors.affiliation: National Research Laboratory of Vascular Biology and Stem Cells, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Korea; Graduate School of Medical Science and Engineering, KAIST, Daejeon 305-701, Korea.
authors.forename: Chan
authors.initials: C
authors.lastname: Kim
authors.affiliation: National Research Laboratory of Vascular Biology and Stem Cells, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Korea; Graduate School of Medical Science and Engineering, KAIST, Daejeon 305-701, Korea.
authors.forename: Hanseul
authors.initials: H
authors.lastname: Yang
authors.affiliation: Division of Vascular Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Fukushima
authors.affiliation: Department of Biological Sciences, KAIST, Daejeon 305-701, Korea.
authors.forename: Phei Er
authors.initials: PE
authors.lastname: Saw
authors.affiliation: National Research Laboratory of Vascular Biology and Stem Cells, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Korea; Graduate School of Medical Science and Engineering, KAIST, Daejeon 305-701, Korea.
authors.forename: Junyeop
authors.initials: J
authors.lastname: Lee
authors.affiliation: National Research Laboratory of Vascular Biology and Stem Cells, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Korea; Graduate School of Medical Science and Engineering, KAIST, Daejeon 305-701, Korea.
authors.forename: Jin-Sung
authors.initials: JS
authors.lastname: Park
authors.affiliation: National Research Laboratory of Vascular Biology and Stem Cells, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Korea; Graduate School of Medical Science and Engineering, KAIST, Daejeon 305-701, Korea.
authors.forename: Intae
authors.initials: I
authors.lastname: Park
authors.affiliation: Department of Bio and Brain Engineering, KAIST, Daejeon 305-701, Korea.
authors.forename: Jinmyung
authors.initials: J
authors.lastname: Jung
authors.affiliation: Laboratory for Stem Cell Biology, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kataoka
authors.affiliation: Department of Bio and Brain Engineering, KAIST, Daejeon 305-701, Korea.
authors.forename: Doheon
authors.initials: D
authors.lastname: Lee
authors.affiliation: Department of Biological Sciences, KAIST, Daejeon 305-701, Korea.
authors.forename: Won Do
authors.initials: WD
authors.lastname: Heo
authors.affiliation: National Research Laboratory of Vascular Biology and Stem Cells, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Korea; Graduate School of Medical Science and Engineering, KAIST, Daejeon 305-701, Korea.
authors.forename: Injune
authors.initials: I
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, KAIST, Daejeon 305-701, Korea.
authors.forename: Sangyong
authors.initials: S
authors.lastname: Jon
authors.affiliation: Department of Tissue Morphogenesis, Max-Planck-Institute of Molecular Biomedicine, 48149 Münster, Germany.
authors.forename: Ralf H
authors.initials: RH
authors.lastname: Adams
authors.affiliation: Laboratory for Stem Cell Biology, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Nishikawa
authors.affiliation: Division of Vascular Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. Electronic address: auemura@med.kobe-u.ac.jp.
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Uemura
authors.affiliation: National Research Laboratory of Vascular Biology and Stem Cells, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Korea; Graduate School of Medical Science and Engineering, KAIST, Daejeon 305-701, Korea. Electronic address: gykoh@kaist.ac.kr.
authors.forename: Gou Young
authors.initials: GY
authors.lastname: Koh
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000098:blood supply / Q000201:enzymology* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000201:enzymology*; D034741:RNA, Small Interfering; D015398:Signal Transduction / Q000187:drug effects; D020741:rho GTP-Binding Proteins / Q000378:metabolism*; D054460:rho-Associated Kinases / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D034741:RNA, Small Interfering; C485944:Rhoj protein, mouse; D054460:rho-Associated Kinases; D020558:GTP Phosphohydrolases; C417188:RHOJ protein, human; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein