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.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / pharmacology
  • Animals
  • GTP Phosphohydrolases / metabolism*
  • Gene Knockdown Techniques
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neoplasms, Experimental / blood supply
  • Neoplasms, Experimental / enzymology*
  • Neoplasms, Experimental / pathology
  • Neovascularization, Pathologic / enzymology*
  • RNA, Small Interfering
  • Signal Transduction / drug effects
  • rho GTP-Binding Proteins / metabolism*
  • rho-Associated Kinases / metabolism
  • rhoA GTP-Binding Protein / metabolism


  • Angiogenesis Inhibitors
  • RNA, Small Interfering
  • Rhoj protein, mouse
  • rho-Associated Kinases
  • GTP Phosphohydrolases
  • RHOJ protein, human
  • rho GTP-Binding Proteins
  • rhoA GTP-Binding Protein