ArticleOncogene2017
Rho-associated kinase 1 inhibition is synthetically lethal with von Hippel-Lindau deficiency in clear cell renal cell carcinoma.
Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 43 citations in OpenAlex.
- VHL synthetic lethality screens uncover CBF-β as a negative regulator of STING.Nature communications · 2026Article
- Renal cell carcinoma organoids for precision medicine: bridging the gap between models and patients.Journal of translational medicine · 2025Review
- ROCK inhibition suppresses glioblastoma via a PTEN-associated reduction in PI3K/AKT signaling.Medical oncology (Northwood, London, England) · 2025Article
- Organoids as Sophisticated Tools for Renal Cancer Research: Extensive Applications and Promising Prospects.Cellular and molecular bioengineering · 2024Review
- Von Hippel-Lindau protein signalling in clear cell renal cell carcinoma.Nature reviews. Urology · 2024Review
- Targeting transforming growth factor-β1 by methylseleninic acid/seleno-L-methionine in clear cell renal cell carcinoma: Mechanisms and therapeutic potential.Cancer treatment and research communications · 2024Article
- Construction methods and latest applications of kidney cancer organoids.Oncology reviews · 2024Review
- Inflammatory Networks in Renal Cell Carcinoma.Cancers · 2023Review
- Rational combinations of targeted cancer therapies: background, advances and challenges.Nature reviews. Drug discovery · 2023Review
- Exploring synthetic lethal network for the precision treatment of clear cell renal cell carcinoma.Scientific reports · 2022Article
- Von Hippel-Lindau tumor suppressor pathways & corresponding therapeutics in kidney cancer.Journal of genetics and genomics = Yi chuan xue bao · 2021Review
- Synapse-specific Lrp4 mRNA enrichment requires Lrp4/MuSK signaling, muscle activity and Wnt non-canonical pathway.Cell & bioscience · 2021Article
- Targeting the HIF2-VEGF axis in renal cell carcinoma.Nature medicine · 2020Review
- Gut Microbiome Critically Impacts PCB-induced Changes in Metabolic Fingerprints and the Hepatic Transcriptome in Mice.Toxicological sciences : an official journal of the Society of Toxicology · 2020Article
- The mProceedings of the National Academy of Sciences of the United States of America · 2020Article
- TBK1 Is a Synthetic Lethal Target in Cancer withCancer discovery · 2020Article
- Targeting the RhoGTPase/ROCK pathway for the treatment of VHL/HIF pathway-driven cancers.Small GTPases · 2020Review
- Article
- Rho kinase inhibitors reduce voltage-dependent CaAmerican journal of physiology. Renal physiology · 2019Article
- HIF-independent synthetic lethality between CDK4/6 inhibition and VHL loss across species.Science signaling · 2019Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Clear cell renal cell carcinoma (CC-RCC) is the most lethal of all genitourinary cancers. The functional loss of the von Hippel-Lindau (VHL) gene occurs in 90% of CC-RCC, driving cancer progression. The objective of this study was to identify chemical compounds that are synthetically lethal with VHL deficiency in CC-RCC. An annotated chemical library, the library of pharmacologically active compounds (LOPAC), was screened in parallel on VHL-deficient RCC4 cells and RCC4VHL cells with re-introduced VHL. The ROCK inhibitor, Y-27632, was identified and validated for selective targeting of VHL-deficient CC-RCC in multiple genetic backgrounds by clonogenic assays. Downregulation of ROCK1 by small interfering RNA (siRNA) selectively reduced the colony-forming ability of VHL-deficient CC-RCC, thus mimicking the effect of Y-27632 treatment, whereas downregulation of ROCK2 had no effect. In addition, two other ROCK inhibitors, RKI 1447 and GSK 429286, selectively targeted VHL-deficient CC-RCC. CC-RCC treatment with ROCK inhibitors is cytotoxic and cytostatic based on bromodeoxyuridine (BrdU) assay, propidium iodide (PI) staining and growth curves, and blocks cell migration based on transwell assay. On the one hand, knockdown of hypoxia-inducible factor (HIF) β in the VHL-deficient CC-RCC had a protective effect against Y-27632 treatment, mimicking VHL reintroduction. On the other hand, CC-RCCVHL cells were sensitized to Y-27632 treatment in hypoxia (2% O
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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.