Evidence map›Paper›PMID 32450824›Full record

ArticleBMC cancer2020

Independence of HIF1a and androgen signaling pathways in prostate cancer.

Maxine G B Tran, Becky A S Bibby, Lingjian Yang, Franklin Lo, Anne Y Warren, Deepa Shukla, Michelle Osborne, James Hadfield, Thomas Carroll, Rory Stark and 7 more

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed, 1 pooled it
3.3field-weighted citation impact, top 6% 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

31 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.

  1. Pooled it
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  14. Hypoxia promotes conversion to a stem cell phenotype in prostate cancer cells by activating HIF-1α/Notch1 signaling pathway.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023
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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

17 authors at 6 institutions in 2 countries.

Maxine G B TranUro-oncology Research Group, Cancer Research UK Cambridge Institute, Cambridge, CB02 0RE, UK.
Becky A S BibbyDivision of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Christie Hospital NHS Trust, M20 4BX, Manchester, UK.
Lingjian YangDivision of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Christie Hospital NHS Trust, M20 4BX, Manchester, UK.
Franklin LoUro-oncology Research Group, Cancer Research UK Cambridge Institute, Cambridge, CB02 0RE, UK.
Anne Y WarrenDepartment of Pathology, Addenbrooke's Cambridge University Hospital, Cambridge, UK.
Deepa ShuklaDivision of Medicine, University College London, London, UK.
Michelle OsborneUro-oncology Research Group, Cancer Research UK Cambridge Institute, Cambridge, CB02 0RE, UK.
James HadfieldUro-oncology Research Group, Cancer Research UK Cambridge Institute, Cambridge, CB02 0RE, UK.
Thomas CarrollUro-oncology Research Group, Cancer Research UK Cambridge Institute, Cambridge, CB02 0RE, UK.
Rory StarkUro-oncology Research Group, Cancer Research UK Cambridge Institute, Cambridge, CB02 0RE, UK.
Helen ScottUro-oncology Research Group, Cancer Research UK Cambridge Institute, Cambridge, CB02 0RE, UK.
Antonio Ramos-MontoyaUro-oncology Research Group, Cancer Research UK Cambridge Institute, Cambridge, CB02 0RE, UK.
Charlie MassieUro-oncology Research Group, Cancer Research UK Cambridge Institute, Cambridge, CB02 0RE, UK.
Patrick MaxwellCambridge Institute of Medical Research, Cambridge Biomedical Campus, Cambridge, CB2 0SP, UK.
Catharine M L WestDivision of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Christie Hospital NHS Trust, M20 4BX, Manchester, UK.
Ian G MillsPatrick G Johnston Centre for Cancer Research and Cell Biology, Queens University Belfast, Belfast, BT9 7AE, UK. ian.mills@nds.ox.ac.uk.ORCID http://orcid.org/0000-0001-5347-5083
David E NealNuffield Department of Surgical Sciences, University of Oxford, Oxford, OX3 9DU, UK.
Cancer Research UK · GBManchester Academic Health Science Centre · GBUniversity of Cambridge · GBQueen's University Belfast · GBThe Royal Free Hospital · GBUniversity College London · GB

Funding

National Institute for Health Research G0500966/75466
6 · The paper itself

Abstract

backgroundTherapeutic targeting of the androgen signaling pathway is a mainstay treatment for prostate cancer. Although initially effective, resistance to androgen targeted therapies develops followed by disease progression to castrate-resistant prostate cancer (CRPC). Hypoxia and HIF1a have been implicated in the development of resistance to androgen targeted therapies and progression to CRCP. The interplay between the androgen and hypoxia/HIF1a signaling axes was investigated.

methodsIn vitro stable expression of HIF1a was established in the LNCaP cell line by physiological induction or retroviral transduction. Tumor xenografts with stable expression of HIF1a were established in castrated and non-castrated mouse models. Gene expression analysis identified transcriptional changes in response to androgen treatment, hypoxia and HIF1a. The binding sites of the AR and HIF transcription factors were identified using ChIP-seq.

resultsAndrogen and HIF1a signaling promoted proliferation in vitro and enhanced tumor growth in vivo. The stable expression of HIF1a in vivo restored tumor growth in the absence of endogenous androgens. Hypoxia reduced AR binding sites whereas HIF binding sites were increased with androgen treatment under hypoxia. Gene expression analysis identified seven genes that were upregulated both by AR and HIF1a, of which six were prognostic.

conclusionsThe oncogenic AR, hypoxia and HIF1a pathways support prostate cancer development through independent signaling pathways and transcriptomic profiles. AR and hypoxia/HIF1a signaling pathways independently promote prostate cancer progression and therapeutic targeting of both pathways simultaneously is warranted.

Indexed as

Gene Expression Regulation, NeoplasticAndrogen AntagonistsAndrogensAnimalsApoptosisBiomarkers, TumorCell ProliferationGene Expression ProfilingHumansHypoxiaHypoxia-Inducible Factor 1, alpha SubunitMaleMiceProstatic NeoplasmsReceptors, AndrogenSignal TransductionAndrogen AntagonistsAndrogensAR protein, humanBiomarkers, TumorHIF1A protein, humanHypoxia-Inducible Factor 1, alpha SubunitReceptors, AndrogenAndrogen signalingHIF1a signalingHypoxiaProstate cancer

Identifiers

PMID32450824
PMCPMC7249645
OpenAlexW3026108160

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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.