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Vascular RhoJ Is an Effective and Selective Target for Tumor Angiogenesis and Vascular Disruption
Open accessAbstract
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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“Gen RHOJ encodes one of many small proteins of the Rho family that bind GTP (guanosine-5′-triphosphate), which acts as an energy transporter in the cell.”
From Endometriosis: Epidemiology, Classification, Pathogenesis, Treatment and Genetics (Review of Literature) (2021) · cites this paper as [190]
In the citing paper
“Rho proteins regulate the dynamic assembly of cytoskeleton components in several physiological processes, such as cell proliferation and motility.”
From Endometriosis: Epidemiology, Classification, Pathogenesis, Treatment and Genetics (Review of Literature) (2021) · cites this paper as [190]
In the citing paper
“The protein encoded by the RHOJ gene is activated by vascular endothelial growth factor and can regulate angiogenesis and also plays an important role in adipocyte differentiation, endothelial motility, and cytoskeletal formation [190].”
From Endometriosis: Epidemiology, Classification, Pathogenesis, Treatment and Genetics (Review of Literature) (2021) · cites this paper as [190]
In the citing paper
“Rho are also involved in cancer transformation and metastasis.”
From Endometriosis: Epidemiology, Classification, Pathogenesis, Treatment and Genetics (Review of Literature) (2021) · cites this paper as [190]
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Metadata
- Authors
- Kim, C., Yang, H., Fukushima, Y., Saw, P. E., Lee, J., Park, J.-S., Park, I., Jung, J., Kataoka, H., Lee, D., Do Heo, W., Kim, I., Jon, S., Adams, R. H., Nishikawa, S.-I., Uemura, A., & Koh, G. Y.
- Affiliations
- Korea Advanced Institute of Science and Technology (KR)
- Kobe University (JP)
- RIKEN (JP)
- Max Planck Institute for Molecular Biomedicine (DE)
- Corresponding author
- Uemura, Akiyoshi
- Koh, Gou Young
- ORCID
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2014-01
- Volume
- 25
- Issue
- 1
- Pages
- 102-117
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W2068757005
- Cited by
- 131
- References
- 44
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 10 · 2023: 15 · 2022: 7 · 2021: 12 · 2020: 19 · 2019: 12 · 2018: 7 · 2017: 13 · 2016: 12 · 2015: 8 · 2014: 5
- FWCI
- 5.19
- Type
- journal article
- Language
- en
- Update notices
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
- Keywords
- RhoJ, Rho GTPases, tumor angiogenesis, vascular disruption, tumor vasculature, RhoA/ROCK signaling, Rho kinase, tumor endothelial cells, anti-angiogenic therapy, combination therapy, chemotherapy, vascular disrupting agents, tumor progression
- MeSH terms
- Animals, Humans, Mice, Inbred C57BL, Mice, Transgenic, Neoplasms, Experimental, Neovascularization, Pathologic, Signal Transduction, Angiogenesis Inhibitors, GTP Phosphohydrolases, rho GTP-Binding Proteins, rhoA GTP-Binding Protein, RNA, Small Interfering, Mice, rho-Associated Kinases, Gene Knockdown Techniques
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