ArticleCancer biology & therapy2015
Hierarchical paracrine interaction of breast cancer associated fibroblasts with cancer cells via hMAPK-microRNAs to drive ER-negative breast cancer phenotype.
Article in Cancer biology & therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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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.
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Who cites it
48 citing papers in PubMed, 63 citations in OpenAlex.
- In vivo exposure to CXCL12-high CAFs and chronic CXCL12 stimulation in vitro is sufficient to enhance metastasis of ER-positive breast cancer.Breast cancer research and treatment · 2026Article
- CAF-derived exosomes: orchestrators of dysregulated signaling pathways in breast cancer progression.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- The role of MiRNA-mediated tumor microenvironment in bone metastasis from a multi-omics perspective: cross-cancer mechanisms and clinical translation.Frontiers in oncology · 2026Review
- Fibroblasts activated by miRs-185-5p, miR-652-5p, and miR-1246 shape the tumor microenvironment in triple-negative breast cancer via PATZ1 downregulation.Cellular and molecular life sciences : CMLS · 2025Article
- Small molecule inhibitors of hnRNPA2B1-RNA interactions reveal a predictable sorting of RNA subsets into extracellular vesicles.Nucleic acids research · 2025Article
- The role of exosomal non-coding RNAs in the breast cancer tumor microenvironment.Functional & integrative genomics · 2025Review
- Relationship between exosomes and cancer: formation, diagnosis, and treatment.International journal of biological sciences · 2025Review
- Roles of miR-20a-5p in breast cancer based on the clinical and multi-omic (CAMO) cohort and in vitro studies.Scientific reports · 2024Article
- MicroRNAs mediated interaction of tumor microenvironment cells with breast cancer cells during bone metastasis.Breast cancer (Tokyo, Japan) · 2023Review
- Deciphering the Functional Status of Breast Cancers through the Analysis of Their Extracellular Vesicles.International journal of molecular sciences · 2023Review
- Exosome-transmitted circMolecular and cellular biology · 2023Article
- Tumor-derived exosomal non-coding RNAs as diagnostic biomarkers in cancer.Cellular and molecular life sciences : CMLS · 2022Review
- Spotlight on Exosomal Non-Coding RNAs in Breast Cancer: An In Silico Analysis to Identify Potential lncRNA/circRNA-miRNA-Target Axis.International journal of molecular sciences · 2022Review
- Cancer-associated fibroblasts in breast cancer: Challenges and opportunities.Cancer communications (London, England) · 2022Review
- Extracellular Vesicles as Mediators of Therapy Resistance in the Breast Cancer Microenvironment.Biomolecules · 2022Review
- Breast Cancer CAFs: Spectrum of Phenotypes and Promising Targeting Avenues.International journal of molecular sciences · 2021Review
- Review
- Article
- Cancer-associated fibroblast-derived SDF-1 induces epithelial-mesenchymal transition of lung adenocarcinoma via CXCR4/β-catenin/PPARδ signalling.Cell death & disease · 2021Article
- Exosomal miRNAs and lncRNAs: The Modulator Keys of Cancer-Associated Fibroblasts in the Genesis and Progression of Malignant Neoplasms.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multiple juxtacrine and paracrine interactions occur between cancer cells and non-cancer cells of the tumor microenvironment (TME) that direct tumor progression. Cancer Associated Fibroblasts (CAFs) are an integral component of the TME, and the majority of breast tumor stroma is comprised of CAFs. Heterotypic interactions between cancer cells and non-cancer cells of the TME occur via soluble agents, including cytokines, hormones, growth factors, and secreted microRNAs. We previously identified a microRNA signature indicative of hyperactive MAPK signaling (hMAPK-miRNA signature) that significantly associated with reduced recurrence-free and overall survival. Here we report that the hMAPK-miRNA signature associates with a high metric of stromal cell infiltrate, and we investigate the role of microRNAs, particularly hMAPK-microRNAs, secreted by CAFs on estrogen receptor (ER) expression in breast cancer cells. ER-positive MCF-7/ltE2- cells were treated with conditioned media (CM) from CAFs derived from breast cancers of different PAM50 subtypes (CAFBAS, CAFHER2, and CAFLA). CAF CM isolated specifically from ER-negative primary breast tumors led to ER repression in vitro. Nanoparticle tracking analysis and transmission electron microscopy confirmed the presence of CAF-secreted exosomes in CM and the uptake of these exosomes by the ER+ MCF-7/ltE2- cells. Differentially expressed microRNAs in CAF CM as well as in MCF-7/ltE2- cells treated with this CM were identified. Knockdown of miR-221/222 in CAFBAS resulted in knockdown of miR221/222 levels in the conditioned media and the CM from CAFBAS; miR221/222 knockdown rescued ER repression in ER-positive cell lines treated with CAFBAS-CM. Collectively, our results demonstrate that CAF-secreted microRNAs are directly involved in ER-repression, and may contribute to the MAPK-induced ER repression in breast cancer cells.
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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.