ArticleNature medicine2013
Epigenetic expansion of VHL-HIF signal output drives multiorgan metastasis in renal cancer.
Article in Nature medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 145 papers.
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Who cites it
145 citing papers in PubMed, 219 citations in OpenAlex.
- Dynamic epigenetic changes to VHL occur with sunitinib in metastatic clear cell renal cancer.Oncotarget · 2016Trial
- A CTC/DTC-centered temporal framework of bone metastasis: From dissemination to dormancy and reactivation.Journal of bone oncology · 2026Review
- Racial and ethnic disparities in the cause of death for clear cell renal cell carcinoma.Nature communications · 2026Article
- Perturbation of BRD4 and p300 activity suppresses super enhancer‑drivenOncology reports · 2026Article
- ODF3B Promotes the Progression of Clear Cell Renal Cell Carcinoma via the JAK/STAT Signaling Pathway.Medical science monitor : international medical journal of experimental and clinical research · 2026Article
- MAGI3 deficiency unleashes β-catenin conformational change to drive metastatic progression and mTOR inhibitor resistance in ccRCC.Cell death & disease · 2026Article
- Mechanisms of resistance to VHL loss-induced genetic and pharmacological vulnerabilities.EMBO molecular medicine · 2026Article
- BCL-XbioRxiv : the preprint server for biology · 2025Article
- The SLC1A1/EAAT3 dicarboxylic amino acid transporter is an epigenetically dysregulated nutrient carrier that sustains oncogenic metabolic programs.Nature communications · 2025Article
- Tumour sampling conditions perturb the metabolic landscape of clear cell renal cell carcinoma.Nature communications · 2025Article
- Comparative single-cell transcriptomic profiling of patient-derived renal carcinoma cells in cellular and animal models of kidney cancer.FEBS open bio · 2025Article
- The RNA demethylase FTO promotes glutamine metabolism in clear cell renal cell carcinoma through the regulation of SLC1A5.Science advances · 2025Article
- SWI/SNF ATPase silenced HLF potentiates lung metastasis in solid cancers.Nature communications · 2025Article
- Biomarker-informed care for patients with renal cell carcinoma.Nature cancer · 2025Review
- Activation of RHO-GTPase gene pattern correlates with adverse clinical outcome and immune microenvironment in clear cell renal cell carcinoma.Clinical and experimental medicine · 2025Article
- New players in the landscape of renal cell carcinoma bone metastasis and therapeutic opportunities.International journal of cancer · 2025Review
- Epigenetic regulation in cancer.MedComm · 2024Review
- Construction and validation of a chromatin regulator-related gene signature for prognostic and therapeutic significance of clear cell renal cell carcinoma.Translational cancer research · 2024Article
- Cancer Evolution: A Multifaceted Affair.Cancer discovery · 2024Article
- Targeting GABARAPL1/HIF-2a axis to induce tumor cell apoptosis in nasopharyngeal carcinoma.Iranian journal of basic medical sciences · 2024Article
85 more citing papers are in PubMed but not listed here.
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10 authors at 3 institutions in 1 country.
Funding
Abstract
Inactivation of the von Hippel-Lindau tumor suppressor gene, VHL, is an archetypical tumor-initiating event in clear cell renal carcinoma (ccRCC) that leads to the activation of hypoxia-inducible transcription factors (HIFs). However, VHL mutation status in ccRCC is not correlated with clinical outcome. Here we show that during ccRCC progression, cancer cells exploit diverse epigenetic alterations to empower a branch of the VHL-HIF pathway for metastasis, and the strength of this activation is associated with poor clinical outcome. By analyzing metastatic subpopulations of VHL-deficient ccRCC cells, we discovered an epigenetically altered VHL-HIF response that is specific to metastatic ccRCC. Focusing on the two most prominent pro-metastatic VHL-HIF target genes, we show that loss of Polycomb repressive complex 2 (PRC2)-dependent histone H3 Lys27 trimethylation (H3K27me3) activates HIF-driven chemokine (C-X-C motif) receptor 4 (CXCR4) expression in support of chemotactic cell invasion, whereas loss of DNA methylation enables HIF-driven cytohesin 1 interacting protein (CYTIP) expression to protect cancer cells from death cytokine signals. Thus, metastasis in ccRCC is based on an epigenetically expanded output of the tumor-initiating pathway.
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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.