ArticleOncotarget2016
TRPV4 channels regulate tumor angiogenesis via modulation of Rho/Rho kinase pathway.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
61 citing papers in PubMed, 90 citations in OpenAlex.
- Compressive stress-driven Piezo1 activation and Rho-ROCK mechanotransduction promote tumor progression via epigenetic mechanical memory.Science advances · 2026Article
- Stromal cells contribute to progression, recurrence, and metastasis in oral squamous cell carcinoma: a call for therapy.Journal of translational medicine · 2026Review
- The role of TRPV4 in ischemic stroke.Molecular brain · 2026Review
- Transient receptor potential vanilloid type 4 channels mediate bladder cancer cell proliferation, migration, and chemoresistance.The Journal of pharmacology and experimental therapeutics · 2025Article
- TRPV4 drives the progression of leiomyosarcoma by promoting ECM1 generation and co-activating the FAK/PI3K/AKT/GSK3β pathway.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Research progress on the role of biomechanical clues in the progression of lung cancer.Frontiers in cell and developmental biology · 2025Review
- Prostaglandin E2 dependent migration of human brain endothelial cells is mediated through Rho-Kinase-II.PloS one · 2025Article
- Recent advances on the structure and the function relationships of the TRPV4 ion channel.Channels (Austin, Tex.) · 2024Review
- Structural Pharmacology of TRPV4 Antagonists.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Targeting TRPV4 Channels for Cancer Pain Relief.Cancers · 2024Review
- A TRP to Pathological Angiogenesis and Vascular Normalization.Comprehensive Physiology · 2024Review
- Mechanosensitive TRPV4 channel guides maturation and organization of the bilayered mammary epithelium.Scientific reports · 2024Article
- Studying Angiogenesis Using Matrigel In Vitro and In Vivo.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Deletion of Endothelial TRPV4 Protects Heart From Pressure Overload-Induced Hypertrophy.Hypertension (Dallas, Tex. : 1979) · 2023Article
- TRPV4-Rho GTPase complex structures reveal mechanisms of gating and disease.Nature communications · 2023Article
- Combination Therapy as a Promising Way to Fight Oral Cancer.Pharmaceutics · 2023Review
- Six Decades of History of Hypertension Research at the University of Toledo: Highlighting Pioneering Contributions in Biochemistry, Genetics, and Host-Microbiota Interactions.Current hypertension reports · 2022Review
- Transient Receptor Potential (TRP) Channels in Tumor Vascularization.International journal of molecular sciences · 2022Review
- WNK1-OSR1 Signaling Regulates Angiogenesis-Mediated Metastasis towards Developing a Combinatorial Anti-Cancer Strategy.International journal of molecular sciences · 2022Article
- Biomimetic Hydrogels in the Study of Cancer Mechanobiology: Overview, Biomedical Applications, and Future Perspectives.Gels (Basel, Switzerland) · 2022Review
1 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Targeting angiogenesis is considered a promising therapy for cancer. Besides curtailing soluble factor mediated tumor angiogenesis, understanding the unexplored regulation of angiogenesis by mechanical cues may lead to the identification of novel therapeutic targets. We have recently shown that expression and activity of mechanosensitive ion channel transient receptor potential vanilloid 4 (TRPV4) is suppressed in tumor endothelial cells and restoring TRPV4 expression or activation induces vascular normalization and improves cancer therapy. However, the molecular mechanism(s) by which TRPV4 modulates angiogenesis are still in their infancy. To explore how TRPV4 regulates angiogenesis, we have employed TRPV4 null endothelial cells (TRPV4KO EC) and TRPV4KO mice. We found that absence of TRPV4 (TRPV4KO EC) resulted in a significant increase in proliferation, migration, and abnormal tube formation in vitro when compared to WT EC. Concomitantly, sprouting angiogenesis ex vivo and vascular growth in vivo was enhanced in TRPV4KO mice. Mechanistically, we observed that loss of TRPV4 leads to a significant increase in basal Rho activity in TRPV4KO EC that corresponded to their aberrant mechanosensitivity on varying stiffness ECM gels. Importantly, pharmacological inhibition of the Rho/Rho kinase pathway by Y-27632 normalized abnormal mechanosensitivity and angiogenesis exhibited by TRPV4KO EC in vitro. Finally, Y-27632 treatment increased pericyte coverage and in conjunction with Cisplatin, significantly reduced tumor growth in TRPV4KO mice. Taken together, these data suggest that TRPV4 regulates angiogenesis endogenously via modulation of EC mechanosensitivity through the Rho/Rho kinase pathway and can serve as a potential therapeutic target for cancer therapy.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.