ArticleOncogene2016
Activation of mechanosensitive ion channel TRPV4 normalizes tumor vasculature and improves cancer therapy.
Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
What it found
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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.
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Who cites it
91 citing papers in PubMed, 151 citations in OpenAlex.
- Mechanobiology of solid tumor vasculature: implications for tumor progression.Cancer metastasis reviews · 2026Review
- Article
- Integration of cAMP and TRPV4 Signaling to Optimize Collagen Remodeling for Management of Fibrosis.Cells · 2025Review
- Enhancing cancer therapyLab on a chip · 2025Article
- Targeting Ion Channels for Cancer Therapy: From Pathophysiological Mechanisms to Clinical Translation.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Transient receptor potential vanilloid type 4 channels mediate bladder cancer cell proliferation, migration, and chemoresistance.The Journal of pharmacology and experimental therapeutics · 2025Article
- Calcium channels as pharmacological targets for cancer therapy.Clinical and experimental medicine · 2025Review
- Metal Ion Signaling in Biomedicine.Chemical reviews · 2025Review
- Research progress on the role of biomechanical clues in the progression of lung cancer.Frontiers in cell and developmental biology · 2025Review
- Micro- and Macronutrients in Endometrial Cancer-From Metallomic Analysis to Improvements in Treatment Strategies.International journal of molecular sciences · 2024Review
- Navigating tumor angiogenesis: therapeutic perspectives and myeloid cell regulation mechanism.Angiogenesis · 2024Review
- Function and mechanism of action of the TRPV1 channel in the development of triple-negative breast cancer.Acta biochimica et biophysica Sinica · 2024Review
- A TRP to Pathological Angiogenesis and Vascular Normalization.Comprehensive Physiology · 2024Review
- Inflammation-induced TRPV4 channels exacerbate blood-brain barrier dysfunction in multiple sclerosis.Journal of neuroinflammation · 2024Article
- Impact of TRP Channels on Extracellular Matrix Remodeling: Focus on TRPV4 and Collagen.International journal of molecular sciences · 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
- Proton-sensing ion channels, GPCRs and calcium signaling regulated by them: implications for cancer.Frontiers in cell and developmental biology · 2024Review
- Microglial activation in spaceflight and microgravity: potential risk of cognitive dysfunction and poor neural health.Frontiers in cellular neuroscience · 2024Review
- Angiotensin II induces endothelial dysfunction and vascular remodeling by downregulating TRPV4 channels.Journal of molecular and cellular cardiology plus · 2023Article
31 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
12 authors at 8 institutions in 1 country.
Funding
Abstract
Tumor vessels are characterized by abnormal morphology and hyperpermeability that together cause inefficient delivery of chemotherapeutic agents. Although vascular endothelial growth factor has been established as a critical regulator of tumor angiogenesis, the role of mechanical signaling in the regulation of tumor vasculature or tumor endothelial cell (TEC) function is not known. Here we show that the mechanosensitive ion channel transient receptor potential vanilloid 4 (TRPV4) regulates tumor angiogenesis and tumor vessel maturation via modulation of TEC mechanosensitivity. We found that TECs exhibit reduced TRPV4 expression and function, which is correlated with aberrant mechanosensitivity towards extracellular matrix stiffness, increased migration and abnormal angiogenesis by TEC. Further, syngeneic tumor experiments revealed that the absence of TRPV4 induced increased vascular density, vessel diameter and reduced pericyte coverage resulting in enhanced tumor growth in TRPV4 knockout mice. Importantly, overexpression or pharmacological activation of TRPV4 restored aberrant TEC mechanosensitivity, migration and normalized abnormal angiogenesis in vitro by modulating Rho activity. Finally, a small molecule activator of TRPV4, GSK1016790A, in combination with anticancer drug cisplatin, significantly reduced tumor growth in wild-type mice by inducing vessel maturation. Our findings demonstrate TRPV4 channels to be critical regulators of tumor angiogenesis and represent a novel target for anti-angiogenic and vascular normalization therapies.
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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.