2. Academic Validation
  3. Vascular RhoJ is an effective and selective target for tumor angiogenesis and vascular disruption

Vascular RhoJ is an effective and selective target for tumor angiogenesis and vascular disruption

  • Cancer Cell. 2014 Jan 13;25(1):102-17. doi: 10.1016/j.ccr.2013.12.010.
Chan Kim 1,  Hanseul Yang 1,  Yoko Fukushima 2,  Phei Er Saw 3,  Junyeop Lee 1,  Jin-Sung Park 1,  Intae Park 1,  Jinmyung Jung 4,  Hiroshi Kataoka 5,  Doheon Lee 4,  Won Do Heo 3,  Injune Kim 1,  Sangyong Jon 3,  Ralf H Adams 6,  Shin-Ichi Nishikawa 5,  Akiyoshi Uemura 7,  Gou Young Koh 8
Affiliations

Affiliations

  • 1 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.
  • 2 Division of Vascular Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
  • 3 Department of Biological Sciences, KAIST, Daejeon 305-701, Korea.
  • 4 Department of Bio and Brain Engineering, KAIST, Daejeon 305-701, Korea.
  • 5 Laboratory for Stem Cell Biology, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.
  • 6 Department of Tissue Morphogenesis, Max-Planck-Institute of Molecular Biomedicine, 48149 Münster, Germany.
  • 7 Division of Vascular Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. Electronic address: [email protected].
  • 8 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: [email protected].
PMID: 24434213 DOI: 10.1016/j.ccr.2013.12.010
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.

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