Evidence map›Paper›PMID 30692202›Full record

ArticleGenes & development2019

CD44 splice isoform switching determines breast cancer stem cell state.

Honghong Zhang, Rhonda L Brown, Yong Wei, Pu Zhao, Sali Liu, Xuan Liu, Yu Deng, Xiaohui Hu, Jing Zhang, Xin D Gao and 4 more

Open access · diamondAbstract read
In one paragraph

Article in Genes & development, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 147 papers.

0numbers the graph read from it
0cells of the map it votes in
147citing papers in PubMed
–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

147 citing papers in PubMed, 222 citations in OpenAlex.

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  14. STAT3 axis in cancer and cancer stem cells: From oncogenesis to targeted therapies.Biochimica et biophysica acta. Reviews on cancer · 2025
    Review
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87 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

14 authors at 4 institutions in 1 country.

Honghong Zhang *Lester and Sue Smith Breast Center, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
Rhonda L Brown *Department of Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
Yong WeiDepartment of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA.
Pu ZhaoLester and Sue Smith Breast Center, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
Sali LiuLester and Sue Smith Breast Center, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
Xuan LiuLester and Sue Smith Breast Center, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
Yu DengLester and Sue Smith Breast Center, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
Xiaohui HuLester and Sue Smith Breast Center, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
Jing ZhangLester and Sue Smith Breast Center, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
Xin D GaoDepartment of Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
Yibin KangDepartment of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA.
Arthur M MercurioDepartment of Molecular, Cell, and Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Hira Lal GoelDepartment of Molecular, Cell, and Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Chonghui ChengLester and Sue Smith Breast Center, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
Baylor College of Medicine · USRobert H. Lurie Comprehensive Cancer Center of Northwestern UniversityPrinceton University · USUniversity of Massachusetts Chan Medical School · US

Funding

TRAINING PROGRAM IN ONCOGENESIS &DEVELOPMENT BIOLOGYT32CA080621 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI EKLUND, ELIZABETH ANN · 2001 to 2018
$4.1M
Integrin splicing and cancer stem cell fateR01CA203439 · NCI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI MERCURIO, ARTHUR M · 2016 to 2020
$1.9M
Investigating the mechanisms of CD44s splice isoform in breast cancer metastasisR01CA182467 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI CHENG, CHONGHUI · 2014 to 2018
$1.6M
Mechanisms of hnRNPM in Alternative Splicing Regulation During EMTR01GM110146 · NIGMS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI CHENG, CHONGHUI · 2014 to 2018
$1.5M
NCI NIH HHS R01 CA182467NCI NIH HHS R01 CA203439NCI NIH HHS T32 CA080621NIGMS NIH HHS R01 GM110146
6 · The paper itself

Abstract

Although changes in alternative splicing have been observed in cancer, their functional contributions still remain largely unclear. Here we report that splice isoforms of the cancer stem cell (CSC) marker CD44 exhibit strikingly opposite functions in breast cancer. Bioinformatic annotation in patient breast cancer in The Cancer Genome Atlas (TCGA) database reveals that the CD44 standard splice isoform (CD44s) positively associates with the CSC gene signatures, whereas the CD44 variant splice isoforms (CD44v) exhibit an inverse association. We show that CD44s is the predominant isoform expressed in breast CSCs. Elimination of the CD44s isoform impairs CSC traits. Conversely, manipulating the splicing regulator ESRP1 to shift alternative splicing from CD44v to CD44s leads to an induction of CSC properties. We further demonstrate that CD44s activates the PDGFRβ/Stat3 cascade to promote CSC traits. These results reveal CD44 isoform specificity in CSC and non-CSC states and suggest that alternative splicing provides functional gene versatility that is essential for distinct cancer cell states and thus cancer phenotypes.

Indexed as

Alternative SplicingAnimalsBreast NeoplasmsCell Line, TumorDisease Models, AnimalFemaleGene Expression Regulation, NeoplasticHumansHyaluronan ReceptorsMiceNeoplastic Stem CellsProtein IsoformsSignal TransductionCD44 protein, humanHyaluronan ReceptorsProtein Isoformsalternative splicingbreast cancerCD44sCSCPDGFRβ/Stat3

Identifiers

PMID30692202
PMCPMC6362815
OpenAlexW2914396082

What OpenQuestion holds

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LicenceCC BY-NC
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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.