ArticleNeoplasia (New York, N.Y.)2012
Lack of a functional VHL gene product sensitizes renal cell carcinoma cells to the apoptotic effects of the protein synthesis inhibitor verrucarin A.
Article in Neoplasia (New York, N.Y.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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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.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
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- Decoding Ribosome Heterogeneity: A New Horizon in Cancer Therapy.Biomedicines · 2024Review
- Glucocorticoids enhance chemotherapy-driven stress granule assembly and impair granule dynamics, leading to cell death.Journal of cell science · 2022Article
- Article
- Targeted EV to Deliver Chemotherapy to Treat Triple-Negative Breast Cancers.Pharmaceutics · 2022Article
- Stress Granules in the Anti-Cancer Medications Mechanism of Action: A Systematic Scoping Review.Frontiers in oncology · 2021Article
- Dual-Targeted Extracellular Vesicles to Facilitate Combined Therapies for Neuroendocrine Cancer Treatment.Pharmaceutics · 2020Article
- Next Generation Sequencing in Renal Cell Carcinoma: Towards Precision Medicine.Kidney cancer journal : official journal of the Kidney Cancer Association · 2019Article
- Targeting the Mevalonate Pathway Suppresses VHL-Deficient CC-RCC through an HIF-Dependent Mechanism.Molecular cancer therapeutics · 2018Article
- Rho-associated kinase 1 inhibition is synthetically lethal with von Hippel-Lindau deficiency in clear cell renal cell carcinoma.Oncogene · 2017Article
- VHL, the story of a tumour suppressor gene.Nature reviews. Cancer · 2015Review
- 5-Fluorouracil affects assembly of stress granules based on RNA incorporation.Nucleic acids research · 2014Article
- Cancer subclonal genetic architecture as a key to personalized medicine.Neoplasia (New York, N.Y.) · 2013Article
- Overcoming intratumor heterogeneity of polygenic cancer drug resistance with improved biomarker integration.Neoplasia (New York, N.Y.) · 2012Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
Abstract
Verrucarin A (VA) is a small molecule derived from the fungal plant pathogen Myrothecium verrucaria and was identified as a selective inhibitor of clear cell renal cell carcinoma (CCRCC) cell proliferation in a high-throughput screen of a library of naturally occurring small molecules. CCRCC arises as a result of loss-of-function mutations in the von Hippel-Lindau (VHL) gene. Here we show that VA inhibits protein translation initiation culminating in apoptosis through the extrinsic signaling pathway. Reintroduction of the VHL gene in CCRCC cells afforded resistance to VA's apoptotic effects. This resistance is mediated in part by the formation of stress granules that entrap signaling molecules that initiate the apoptotic signaling cascade. The VHL gene product was found to be a component of stress granules that develop as result of VA treatment. These findings reveal an important role for the VHL gene product in cytotoxic stress response and have important implications for the rational development of VA-related compounds in chemotherapeutic targeting of CCRCC.
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