Evidence map›Paper›PMID 40866413›Full record

ArticleNature communications2025

Hypoxic stress incites HIF1α-driven ribosome biogenesis that can be exploited by targeting RNA Polymerase I.

Amr Elhamamsy, Brandon J Metge, Courtney A Swain, Mohamed H Elbahoty, Dominique C Hinshaw, Sarah C Kammerud, Dongquan Chen, Rajeev S Samant, Lalita A Shevde

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, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed, 1 pooled it
–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 synthesis or guideline pooled it.

  1. Pooled it
  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

9 authors.

Amr ElhamamsyDepartment of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.ORCID http://orcid.org/0000-0001-8579-0184
Brandon J MetgeDepartment of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.ORCID http://orcid.org/0000-0001-8615-2934
Courtney A SwainDepartment of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.ORCID http://orcid.org/0000-0002-5671-0218
Mohamed H ElbahotyDepartment of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.ORCID http://orcid.org/0000-0001-8766-4616
Dominique C HinshawDepartment of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.
Sarah C KammerudDepartment of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.ORCID http://orcid.org/0000-0002-4808-1618
Dongquan ChenDivision of Preventive Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Rajeev S SamantDepartment of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA. lsamant@uab.edu.
Lalita A ShevdeDepartment of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA. lalitasamant@uabmc.edu.ORCID http://orcid.org/0000-0002-1520-1476

Funding

XRAY CRYSTALLOGRAPHYP30CA013148 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Omer Jamy · 1985 to 2026
$165.9M
NCI NIH HHS P30 CA013148
6 · The paper itself

Abstract

Intratumoral low oxygen tension promotes cancer cell invasion and metastasis. Hypoxia-Inducible Factor 1-alpha (HIF1α) is the principal transcription factor orchestrating cellular responses to hypoxic stress, mediating the regulation of genes implicated in adapting to perturbations in oxygen homeostasis. Here, we describe our findings that functionally demonstrate a nucleolar localization domain in HIF1ɑ that enables HIF1ɑ to translocate to the nucleolus. Nucleolar HIF1ɑ binds the ribosomal DNA promoter and upregulates RNA Polymerase I activity leading to dysregulated ribosomal RNA transcription and consequently enhanced ribosome biogenesis. Ribosome biogenesis is important in supporting cellular metabolic processes and invasion and metastasis. Our findings are recapitulated in breast tumors wherein upregulated HIF1ɑ and rRNA biogenesis are associated with poor prognosis. Finally, our studies demonstrate that inhibition of RNA Polymerase I impedes aggressive traits of hypoxia-driven cancer progression, highlighting the potential of this approach as a therapeutic strategy in breast cancer. Cumulatively our work unravels an unprecedented role of HIF1ɑ in regulating rRNA biogenesis in breast cancer.

Indexed as

Breast NeoplasmsHypoxia-Inducible Factor 1, alpha SubunitRibosomesRNA Polymerase IAnimalsCell HypoxiaCell Line, TumorCell NucleolusDNA, RibosomalFemaleGene Expression Regulation, NeoplasticHumansMicePromoter Regions, GeneticRNA, RibosomalDNA, RibosomalHIF1A protein, humanHypoxia-Inducible Factor 1, alpha SubunitRNA Polymerase IRNA, Ribosomal

Identifiers

PMID40866413
PMCPMC12391393

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.