Evidence map›Paper›PMID 37407568›Full record

ArticleCell death discovery2023

STAT3 and HIF1α cooperatively mediate the transcriptional and physiological responses to hypoxia.

Alberto Dinarello, Riccardo Massimiliano Betto, Linda Diamante, Annachiara Tesoriere, Rachele Ghirardo, Chiara Cioccarelli, Giacomo Meneghetti, Margherita Peron, Claudio Laquatra, Natascia Tiso and 2 more

Open access · goldAbstract read
In one paragraph

Article in Cell death discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed, 1 pooled it
20.2field-weighted citation impact, top 1% of its field
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

41 citing papers in PubMed, 1 synthesis or guideline pooled it, 74 citations in OpenAlex.

  1. Pooled it
  2. Toxics · 2026
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  14. Anoikis: To Die or Not to Die?International journal of molecular sciences · 2026
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  18. Article
  19. STAT3 axis in cancer and cancer stem cells: From oncogenesis to targeted therapies.Biochimica et biophysica acta. Reviews on cancer · 2025
    Review
  20. Review
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

12 authors at 1 institution in 1 country.

Alberto Dinarello *Department of Biology, University of Padova, Padova, Italy.
Riccardo Massimiliano Betto *Department of Molecular Medicine, University of Padova, Padova, Italy.
Linda DiamanteDepartment of Molecular Medicine, University of Padova, Padova, Italy.ORCID http://orcid.org/0000-0002-3268-1707
Annachiara TesoriereDepartment of Biology, University of Padova, Padova, Italy.
Rachele GhirardoDepartment of Biology, University of Padova, Padova, Italy.
Chiara CioccarelliDepartment of Biomedical Sciences, University of Padova, Padova, Italy.
Giacomo MeneghettiDepartment of Biology, University of Padova, Padova, Italy.
Margherita PeronDepartment of Biology, University of Padova, Padova, Italy.
Claudio LaquatraDepartment of Biomedical Sciences, University of Padova, Padova, Italy.
Natascia TisoDepartment of Biology, University of Padova, Padova, Italy.ORCID http://orcid.org/0000-0002-5444-9853
Graziano MartelloDepartment of Biology, University of Padova, Padova, Italy. graziano.martello@unipd.it.
Francesco ArgentonDepartment of Biology, University of Padova, Padova, Italy. francesco.argenton@unipd.it.ORCID http://orcid.org/0000-0002-0803-8236
University of Padua · IT

Funding

Associazione Italiana per la Ricerca sul Cancro (Italian Association for Cancer Research) IG-2017-19928EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council) MetEpiStem
6 · The paper itself

Abstract

STAT3 and HIF1α are two fundamental transcription factors involved in many merging processes, like angiogenesis, metabolism, and cell differentiation. Notably, under pathological conditions, the two factors have been shown to interact genetically, but both the molecular mechanisms underlying such interactions and their relevance under physiological conditions remain unclear. In mouse embryonic stem cells (ESCs) we manage to determine the specific subset of hypoxia-induced genes that need STAT3 to be properly transcribed and, among them, fundamental genes like Vegfa, Hk1, Hk2, Pfkp and Hilpda are worth mentioning. Unexpectedly, we also demonstrated that the absence of STAT3 does not affect the expression of Hif1α mRNA nor the stabilization of HIF1α protein, but the STAT3-driven regulation of the hypoxia-dependent subset of gene could rely on the physical interaction between STAT3 and HIF1α. To further elucidate the physiological roles of this STAT3 non-canonical nuclear activity, we used a CRISPR/Cas9 zebrafish stat3 knock-out line. Notably, hypoxia-related fluorescence of the hypoxia zebrafish reporter line (HRE:mCherry) cannot be induced when Stat3 is not active and, while Stat3 Y705 phosphorylation seems to have a pivotal role in this process, S727 does not affect the Stat3-dependent hypoxia response. Hypoxia is fundamental for vascularization, angiogenesis and immune cells mobilization; all processes that, surprisingly, cannot be induced by low oxygen levels when Stat3 is genetically ablated. All in all, here we report the specific STAT3/HIF1α-dependent subset of genes in vitro and, for the first time with an in vivo model, we determined some of the physiological roles of STAT3-hypoxia crosstalk.

Identifiers

PMID37407568
PMCPMC10323006
OpenAlexW4383163982

What OpenQuestion holds

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LicenceCC BY
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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.