Evidence map›Paper›PMID 34559986›Full record

ArticleCell2021

ERα is an RNA-binding protein sustaining tumor cell survival and drug resistance.

Yichen Xu, Peiwei Huangyang, Ying Wang, Lingru Xue, Emily Devericks, Hao G Nguyen, Xiuyan Yu, Juan A Oses-Prieto, Alma L Burlingame, Sohit Miglani and 2 more

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

Article in Cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
107citing papers in PubMed, 1 pooled it
9.5field-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

107 citing papers in PubMed, 1 synthesis or guideline pooled it, 166 citations in OpenAlex.

  1. Pooled it
  2. SRSF3 plays a key role in liver cancer sex disparity by facilitating hepatocyte expression of ERα and FOXA.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  17. The Interaction ofInternational journal of biological sciences · 2026
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47 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 2 institutions in 2 countries.

Yichen XuDepartment of Urology, University of California, San Francisco, San Francisco, CA 94158, USA; Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Peiwei HuangyangDepartment of Urology, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
Ying WangDepartment of Urology, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
Lingru XueDepartment of Urology, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
Emily DevericksDepartment of Urology, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
Hao G NguyenDepartment of Urology, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
Xiuyan YuDepartment of Breast Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310009, China.
Juan A Oses-PrietoDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
Alma L BurlingameDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
Sohit MiglaniDepartment of Urology, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Biochemistry & Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
Hani GoodarziDepartment of Urology, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Biochemistry & Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
Davide RuggeroDepartment of Urology, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: davide.ruggero@ucsf.edu.
University of California, San Francisco · USSecond Affiliated Hospital of Zhejiang University · CN

Funding

UPR, interferon signaling and tumorigenesisP01CA165997 · NCI · UNIVERSITY OF PENNSYLVANIA · PI DIEHL, JOHN ALAN · 2013 to 2023
$10.9M
Mechanisms of regulated translation control in cancer and its therapeutic implicationsR35CA242986 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI RUGGERO, DAVIDE · 2019 to 2025
$6.4M
Bio-Organic Biomedical Mass Spectromy ResourceP41GM103481 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BURLINGAME, ALMA L · 2012 to 2015
$6.4M
The role of deregulated protein synthesis control in Myc-induced tumorigenesisR01CA140456 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI RUGGERO, DAVIDE · 2009 to 2019
$3.3M
Purchase of Q-Exactive Mass SpectrometerS10OD016229 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BURLINGAME, ALMA L · 2013 to 2013
$507k
NCI NIH HHS P01 CA165997NCI NIH HHS R01 CA140456NCI NIH HHS R35 CA242986NIGMS NIH HHS P41 GM103481NIH HHS S10 OD016229
6 · The paper itself

Abstract

Estrogen receptor α (ERα) is a hormone receptor and key driver for over 70% of breast cancers that has been studied for decades as a transcription factor. Unexpectedly, we discover that ERα is a potent non-canonical RNA-binding protein. We show that ERα RNA binding function is uncoupled from its activity to bind DNA and critical for breast cancer progression. Employing genome-wide cross-linking immunoprecipitation (CLIP) sequencing and a functional CRISPRi screen, we find that ERα-associated mRNAs sustain cancer cell fitness and elicit cellular responses to stress. Mechanistically, ERα controls different steps of RNA metabolism. In particular, we demonstrate that ERα RNA binding mediates alternative splicing of XBP1 and translation of the eIF4G2 and MCL1 mRNAs, which facilitates survival upon stress conditions and sustains tamoxifen resistance of cancer cells. ERα is therefore a multifaceted RNA-binding protein, and this activity transforms our knowledge of post-transcriptional regulation underlying cancer development and drug response.

Indexed as

Drug Resistance, NeoplasmAnimalsBase SequenceBreast NeoplasmsCell Line, TumorCell SurvivalDisease ProgressionEstrogen Receptor alphaEukaryotic Initiation Factor-4GFemaleGene Expression Regulation, NeoplasticGenomicsHumansMiceMice, Inbred NODMyeloid Cell Leukemia Sequence 1 ProteinEIF4G2 protein, humanEstrogen Receptor alphaEukaryotic Initiation Factor-4GMCL1 protein, humanMyeloid Cell Leukemia Sequence 1 ProteinRNA-Binding ProteinsRNA, MessengerTamoxifenX-Box Binding Protein 1XBP1 protein, humanbreast cancercell survivalERαintegrated stress responseRNA-binding proteinRNA splicingtranslation control

Identifiers

PMID34559986
PMCPMC8547373
OpenAlexW3200715289

What OpenQuestion holds

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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.