Evidence map›Paper›PMID 39041201›Full record

ArticleEndocrinology2024

Progesterone Receptor Signaling Promotes Cancer Associated Fibroblast Mediated Tumorigenicity in ER+ Breast Cancer.

Caroline H Diep, Angela Spartz, Thu H Truong, Amy R Dwyer, Dorraya El-Ashry, Carol A Lange

Abstract read
In one paragraph

Article in Endocrinology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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

11 citing papers in PubMed.

  1. Article
  2. Article
  3. Postpartum breast cancer: evidence for a distinct phenotype.Journal of the National Cancer Institute · 2026
    Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Neoplasia in the dromedary camel: a review (Frontiers in veterinary science · 2025
    Review
  10. Article
  11. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors.

Caroline H DiepMasonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.ORCID 0000-0001-9011-6450
Angela SpartzMasonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.
Thu H TruongMasonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.
Amy R DwyerMasonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.ORCID 0000-0002-4422-1433
Dorraya El-AshryDepartment of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.
Carol A LangeMasonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.ORCID 0000-0003-2751-3976

Funding

Progesterone Receptor (PR) Signaling Cross Talk Drives ER+ Breast CancerR01CA229697 · NCI · UNIVERSITY OF MINNESOTA · PI Carol A Lange, Douglas Yee · 2020 to 2026
$3.6M
Department of Defense BC181035NCI NIH HHS R01 CA229697NIH HHS R01 CA229697Tickle Family Land Grant Endowed Chair in Breast Cancer ResearchUniversity of Minnesota University Imaging Centers SCR_020997
6 · The paper itself

Abstract

Breast cancer progression involves intricate interactions between cancer cells and the tumor microenvironment (TME). This study elucidates the critical role of progesterone receptor (PR) signaling in mediating the protumorigenic effects of cancer-associated fibroblasts (CAFs) on estrogen receptor-positive (ER+) luminal breast cancer cells. We demonstrate that CAFs produce physiologically relevant levels of estrogen and progesterone, which significantly contribute to breast cancer tumorigenicity. Specifically, CAF conditioned media (CM) promoted PR-dependent anchorage-independent growth, tumorsphere formation/stem cell expansion, and CD44 upregulation. CAF cells formed co-clusters more frequently with PR+ breast cancer cells relative to PR-null models. While both PR isoforms mediated these actions, PR-A was a dominant driver of tumorsphere formation/stemness, while PR-B induced robust CD44 expression and CAF/tumor cell co-cluster formation. CD44 knockdown impaired CAF/tumor cell co-clustering. Fibroblast growth factor 2 (FGF2), also secreted by CAFs, phosphorylated PR (Ser294) in a MAPK-dependent manner and activated PR to enhance CD44 expression and breast cancer tumorigenicity. The FGF receptor (FGFR) inhibitor PD173074 diminished CAF- and FGF2-dependent PR activation, tumorsphere formation, and co-clustering. In summary, this study reveals a novel mechanism through which stromal CAFs orchestrate elevated PR signaling in ER+ luminal breast cancer via secretion of both progesterone and FGF2, a potent activator of ERK1/2. Understanding tumor cell/TME interactions provides insights into potential therapeutic strategies aimed at disrupting PR- and/or FGF2/FGFR-dependent signaling pathways to prevent early metastasis in patients with ER+ breast cancer.

Indexed as

Breast NeoplasmsCancer-Associated FibroblastsHyaluronan ReceptorsReceptors, EstrogenReceptors, ProgesteroneSignal TransductionAnimalsCarcinogenesisCell Line, TumorCulture Media, ConditionedFemaleFibroblast Growth Factor 2HumansMiceProgesteroneTumor MicroenvironmentCD44 protein, humanCulture Media, ConditionedFibroblast Growth Factor 2Hyaluronan ReceptorsProgesteroneReceptors, EstrogenReceptors, Progesteronebreast cancerCAFFGF2PD173074progesterone

Identifiers

PMID39041201
PMCPMC11492492

What OpenQuestion holds

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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.