Evidence map›Paper›PMID 30655535›Full record

ArticleNature communications2019

ONECUT2 is a driver of neuroendocrine prostate cancer.

Haiyang Guo, Xinpei Ci, Musaddeque Ahmed, Junjie Tony Hua, Fraser Soares, Dong Lin, Loredana Puca, Aram Vosoughi, Hui Xue, Estelle Li and 30 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 172 papers.

0numbers the graph read from it
0cells of the map it votes in
172citing papers in PubMed
20.9field-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

172 citing papers in PubMed, 239 citations in OpenAlex.

  1. Review
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  17. Prostate Cancer: Etiology, Diagnosis, and Treatment.Serican journal of medicine · 2026
    Article
  18. Review
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112 more citing papers are in PubMed but not listed here.

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

40 authors at 10 institutions in 3 countries.

Haiyang GuoPrincess Margaret Cancer Centre, University Health Network, Toronto, M5G 1L7, ON, Canada. allen100006@gmail.com.
Xinpei CiThe Vancouver Prostate Centre, Vancouver General Hospital and Department of Urologic Sciences, The University of British Columbia, Vancouver, V6H 3Z6, BC, Canada.
Musaddeque AhmedPrincess Margaret Cancer Centre, University Health Network, Toronto, M5G 1L7, ON, Canada.
Junjie Tony HuaPrincess Margaret Cancer Centre, University Health Network, Toronto, M5G 1L7, ON, Canada.
Fraser SoaresPrincess Margaret Cancer Centre, University Health Network, Toronto, M5G 1L7, ON, Canada.
Dong LinThe Vancouver Prostate Centre, Vancouver General Hospital and Department of Urologic Sciences, The University of British Columbia, Vancouver, V6H 3Z6, BC, Canada.
Loredana PucaWeill Cornell Medicine, New York, NY, 10065, USA.
Aram VosoughiWeill Cornell Medicine, New York, NY, 10065, USA.
Hui XueThe Vancouver Prostate Centre, Vancouver General Hospital and Department of Urologic Sciences, The University of British Columbia, Vancouver, V6H 3Z6, BC, Canada.
Estelle LiThe Vancouver Prostate Centre, Vancouver General Hospital and Department of Urologic Sciences, The University of British Columbia, Vancouver, V6H 3Z6, BC, Canada.
Peiran SuPrincess Margaret Cancer Centre, University Health Network, Toronto, M5G 1L7, ON, Canada.
Sujun ChenPrincess Margaret Cancer Centre, University Health Network, Toronto, M5G 1L7, ON, Canada.
Tran NguyenPrincess Margaret Cancer Centre, University Health Network, Toronto, M5G 1L7, ON, Canada.
Yi LiangPrincess Margaret Cancer Centre, University Health Network, Toronto, M5G 1L7, ON, Canada.
Yuzhe ZhangPrincess Margaret Cancer Centre, University Health Network, Toronto, M5G 1L7, ON, Canada.
Xin XuPrincess Margaret Cancer Centre, University Health Network, Toronto, M5G 1L7, ON, Canada.
Jing XuPrincess Margaret Cancer Centre, University Health Network, Toronto, M5G 1L7, ON, Canada.
Anjali V SheahanDepartment of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
Wail Ba-AlawiPrincess Margaret Cancer Centre, University Health Network, Toronto, M5G 1L7, ON, Canada.
Si ZhangDepartment of Experimental Therapeutics, BC Cancer Research Centre, Vancouver, V5Z 1L3, BC, Canada.
Osman MahamudPrincess Margaret Cancer Centre, University Health Network, Toronto, M5G 1L7, ON, Canada.
Ravi N VellankiPrincess Margaret Cancer Centre, University Health Network, Toronto, M5G 1L7, ON, Canada.
Martin GleaveThe Vancouver Prostate Centre, Vancouver General Hospital and Department of Urologic Sciences, The University of British Columbia, Vancouver, V6H 3Z6, BC, Canada.
Robert G BristowPrincess Margaret Cancer Centre, University Health Network, Toronto, M5G 1L7, ON, Canada.ORCID http://orcid.org/0000-0002-8553-9544
Benjamin Haibe-KainsPrincess Margaret Cancer Centre, University Health Network, Toronto, M5G 1L7, ON, Canada.
John T PoirierMemorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.ORCID http://orcid.org/0000-0001-9795-5644
Charles M RudinMemorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.ORCID http://orcid.org/0000-0001-5204-3465
Ming-Sound TsaoPrincess Margaret Cancer Centre, University Health Network, Toronto, M5G 1L7, ON, Canada.ORCID http://orcid.org/0000-0002-9160-5405
Bradly G WoutersPrincess Margaret Cancer Centre, University Health Network, Toronto, M5G 1L7, ON, Canada.
Ladan FazliThe Vancouver Prostate Centre, Vancouver General Hospital and Department of Urologic Sciences, The University of British Columbia, Vancouver, V6H 3Z6, BC, Canada.
Felix Y FengDepartment of Radiation Oncology, University of California at San Francisco, San Francisco, CA, 94115, USA.
Leigh EllisDepartment of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.ORCID http://orcid.org/0000-0003-4739-5049
Theo van der KwastPrincess Margaret Cancer Centre, University Health Network, Toronto, M5G 1L7, ON, Canada.
Alejandro BerlinPrincess Margaret Cancer Centre, University Health Network, Toronto, M5G 1L7, ON, Canada.ORCID http://orcid.org/0000-0002-1880-6905
Marianne KoritzinskyPrincess Margaret Cancer Centre, University Health Network, Toronto, M5G 1L7, ON, Canada.
Paul C BoutrosDepartment of Medical Biophysics, University of Toronto, Toronto, M5G 2M9, ON, Canada.ORCID http://orcid.org/0000-0003-0553-7520
Amina ZoubeidiThe Vancouver Prostate Centre, Vancouver General Hospital and Department of Urologic Sciences, The University of British Columbia, Vancouver, V6H 3Z6, BC, Canada.
Himisha BeltranWeill Cornell Medicine, New York, NY, 10065, USA.
Yuzhuo WangThe Vancouver Prostate Centre, Vancouver General Hospital and Department of Urologic Sciences, The University of British Columbia, Vancouver, V6H 3Z6, BC, Canada. ywang@bccrc.ca.ORCID http://orcid.org/0000-0002-9749-8591
Housheng Hansen HePrincess Margaret Cancer Centre, University Health Network, Toronto, M5G 1L7, ON, Canada. Hansenhe@uhnresearch.ca.ORCID http://orcid.org/0000-0003-2898-3363
University Health Network · CAUniversity of British Columbia · CACornell University · USMemorial Sloan Kettering Cancer Center · USOntario Institute for Cancer Research · CABroad Institute · USDana-Farber Cancer Institute · USUniversity of California, San Francisco · USUniversity of Toronto · CAVancouver General Hospital · CA

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
Weill Cornell Medicine (WCM) SPORE in Prostate CancerP50CA211024 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI GUDAS, LORRAINE J · 2017 to 2021
$10.9M
NCI NIH HHS P30 CA008748NCI NIH HHS P50 CA211024
6 · The paper itself

Abstract

Neuroendocrine prostate cancer (NEPC), a lethal form of the disease, is characterized by loss of androgen receptor (AR) signaling during neuroendocrine transdifferentiation, which results in resistance to AR-targeted therapy. Clinically, genomically and epigenetically, NEPC resembles other types of poorly differentiated neuroendocrine tumors (NETs). Through pan-NET analyses, we identified ONECUT2 as a candidate master transcriptional regulator of poorly differentiated NETs. ONECUT2 ectopic expression in prostate adenocarcinoma synergizes with hypoxia to suppress androgen signaling and induce neuroendocrine plasticity. ONEUCT2 drives tumor aggressiveness in NEPC, partially through regulating hypoxia signaling and tumor hypoxia. Specifically, ONECUT2 activates SMAD3, which regulates hypoxia signaling through modulating HIF1α chromatin-binding, leading NEPC to exhibit higher degrees of hypoxia compared to prostate adenocarcinomas. Treatment with hypoxia-activated prodrug TH-302 potently reduces NEPC tumor growth. Collectively, these results highlight the synergy between ONECUT2 and hypoxia in driving NEPC, and emphasize the potential of hypoxia-directed therapy for NEPC patients.

Indexed as

Gene Expression Regulation, NeoplasticAnimalsCarcinogenesisCell HypoxiaCell Line, TumorCell ProliferationDatasets as TopicDisease ProgressionGene Expression ProfilingHomeodomain ProteinsHumansHypoxia-Inducible Factor 1, alpha SubunitMaleMiceMice, Inbred NODMice, SCIDHIF1A protein, humanHomeodomain ProteinsHypoxia-Inducible Factor 1, alpha SubunitNitroimidazolesONECUT2 protein, humanPhosphoramide MustardsRNA, Small InterferingSmad3 ProteinSMAD3 protein, humanTH 302Transcription Factors

Identifiers

PMID30655535
PMCPMC6336817
OpenAlexW2908623381

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.