Evidence map›Paper›PMID 41102155›Full record

ArticleNature communications2025

HIFα isoform specific activities drive cell-type specificity of VHL-associated oncogenesis.

Joanna D C C Lima, Madeleine Hooker, Ran Li, Ayslan B Barros, Norma Masson, Christopher W Pugh, David R Mole, Julie Adam, Peter J Ratcliffe, Samvid Kurlekar

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Joanna D C C LimaLudwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0001-6804-8666
Madeleine HookerLudwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Ran LiNuffield Department of Medicine, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0003-4095-424X
Ayslan B BarrosLudwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Norma MassonLudwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Christopher W PughNuffield Department of Medicine, University of Oxford, Oxford, UK.
David R MoleNuffield Department of Medicine, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-0984-300X
Julie AdamLudwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-7980-7151
Peter J RatcliffeLudwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK. peter.ratcliffe@ndm.ox.ac.uk.ORCID http://orcid.org/0000-0002-2853-806X
Samvid KurlekarLudwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK. samvid.kurlekar@ndm.ox.ac.uk.ORCID http://orcid.org/0000-0003-1633-1827

Funding

Wellcome Trust FC001501
6 · The paper itself

Abstract

Cancers arising from dysregulation of generally operative signaling pathways are often tissue specific, but the mechanisms underlying this paradox are poorly understood. Based on striking cell-type specificity, we postulated that these mechanisms must operate early in cancer development and set out to study them in a model of von Hippel Lindau (VHL) disease. Biallelic mutation of the VHL ubiquitin ligase leads to constitutive activation of hypoxia inducible factors HIF1A and HIF2A and is generally a truncal event in clear cell renal carcinoma. We used an oncogenic tagging strategy in which VHL-mutant cells are marked by tdTomato, enabling their observation, retrieval, and analysis early after VHL-inactivation. Here, we reveal markedly different consequences of HIF1A and HIF2A activation, but that both contribute to renal cell-type specific consequences of VHL-inactivation in the kidney. Early involvement of HIF2A in promoting proliferation within the proximal tubular epithelium supports therapeutic targeting of HIF2A early in VHL disease.

Indexed as

Basic Helix-Loop-Helix ProteinsCarcinogenesisHypoxia-Inducible Factor 1, alpha SubunitKidney Neoplasmsvon Hippel-Lindau DiseaseVon Hippel-Lindau Tumor Suppressor ProteinAnimalsCarcinoma, Renal CellCell ProliferationEndothelial PAS Domain-Containing Protein 1HumansMiceMutationProtein IsoformsBasic Helix-Loop-Helix ProteinsEndothelial PAS Domain-Containing Protein 1Hif1a protein, mouseHypoxia-Inducible Factor 1, alpha SubunitProtein IsoformsVHL protein, humanVHL protein, mouseVon Hippel-Lindau Tumor Suppressor Protein

Identifiers

PMID41102155
PMCPMC12533196

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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.