Evidence map›Paper›PMID 38388711›Full record

ArticleOncogene2024

Cancer-associated fibroblasts rewire the estrogen receptor response in luminal breast cancer, enabling estrogen independence.

Steven E Reid, Jessica Pantaleo, Paulina Bolivar, Matteo Bocci, Jonas Sjölund, Mikkel Morsing, Eugenia Cordero, Sara Larsson, Maria Malmberg, Brinton Seashore-Ludlow and 1 more

Open access · hybridAbstract read
In one paragraph

Article in Oncogene, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 1 pooled it
6.5field-weighted citation impact, top 2% 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

22 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.

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  15. Tumors and their microenvironments: Learning from pediatric brain pathologies.Biochimica et biophysica acta. Reviews on cancer · 2025
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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

11 authors at 2 institutions in 1 country.

Steven E ReidDepartment of Laboratory Medicine, Division of Translational Cancer Research, Lund University Cancer Centre, Medicon Village, Lund University, Lund, Sweden.
Jessica PantaleoDepartment of Laboratory Medicine, Division of Translational Cancer Research, Lund University Cancer Centre, Medicon Village, Lund University, Lund, Sweden.
Paulina BolivarDepartment of Laboratory Medicine, Division of Translational Cancer Research, Lund University Cancer Centre, Medicon Village, Lund University, Lund, Sweden.
Matteo BocciDepartment of Laboratory Medicine, Division of Translational Cancer Research, Lund University Cancer Centre, Medicon Village, Lund University, Lund, Sweden.ORCID 0000-0002-8774-0006
Jonas SjölundDepartment of Laboratory Medicine, Division of Translational Cancer Research, Lund University Cancer Centre, Medicon Village, Lund University, Lund, Sweden.ORCID 0000-0002-6992-3415
Mikkel MorsingDepartment of Laboratory Medicine, Division of Translational Cancer Research, Lund University Cancer Centre, Medicon Village, Lund University, Lund, Sweden.ORCID 0000-0001-8322-8796
Eugenia CorderoDepartment of Laboratory Medicine, Division of Translational Cancer Research, Lund University Cancer Centre, Medicon Village, Lund University, Lund, Sweden.
Sara LarssonDepartment of Laboratory Medicine, Division of Translational Cancer Research, Lund University Cancer Centre, Medicon Village, Lund University, Lund, Sweden.ORCID 0000-0002-0002-0779
Maria MalmbergDepartment of Laboratory Medicine, Division of Translational Cancer Research, Lund University Cancer Centre, Medicon Village, Lund University, Lund, Sweden.
Brinton Seashore-LudlowDepartment of Oncology-Pathology, SciLifeLab, Stockholm, Sweden.
Kristian PietrasDepartment of Laboratory Medicine, Division of Translational Cancer Research, Lund University Cancer Centre, Medicon Village, Lund University, Lund, Sweden. kristian.pietras@med.lu.se.ORCID 0000-0001-6738-4705
Lund University · SEScience for Life Laboratory · SE

Funding

Cancerfonden (Swedish Cancer Society) 211808PjCancerfonden (Swedish Cancer Society) Postdoctoral fellowshipVetenskapsrådet (Swedish Research Council) 2018-03086
6 · The paper itself

Abstract

Advanced breast cancers represent a major therapeutic challenge due to their refractoriness to treatment. Cancer-associated fibroblasts (CAFs) are the most abundant constituents of the tumor microenvironment and have been linked to most hallmarks of cancer. However, the influence of CAFs on therapeutic outcome remains largely unchartered. Here, we reveal that spatial coincidence of abundant CAF infiltration with malignant cells was associated with reduced estrogen receptor (ER)-α expression and activity in luminal breast tumors. Notably, CAFs mediated estrogen-independent tumor growth by selectively regulating ER-α signaling. Whereas most prototypical estrogen-responsive genes were suppressed, CAFs maintained gene expression related to therapeutic resistance, basal-like differentiation, and invasion. A functional drug screen in co-cultures identified effector pathways involved in the CAF-induced regulation of ER-α signaling. Among these, the Transforming Growth Factor-β and the Janus kinase signaling cascades were validated as actionable targets to counteract the CAF-induced modulation of ER-α activity. Finally, genes that were downregulated in cancer cells by CAFs were predictive of poor response to endocrine treatment. In conclusion, our work reveals that CAFs directly control the luminal breast cancer phenotype by selectively modulating ER-α expression and transcriptional function, and further proposes novel targets to disrupt the crosstalk between CAFs and tumor cells to reinstate treatment response to endocrine therapy in patients.

Indexed as

Breast NeoplasmsCancer-Associated FibroblastsEstrogen Receptor alphaEstrogensFemaleHumansReceptors, EstrogenSignal TransductionTumor MicroenvironmentEstrogen Receptor alphaEstrogensReceptors, Estrogen

Identifiers

PMID38388711
PMCPMC10997519
OpenAlexW4392038977

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.