ArticleBritish journal of cancer2021
Inhibition of interferon-signalling halts cancer-associated fibroblast-dependent protection of breast cancer cells from chemotherapy.
Article in British journal of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 47 citations in OpenAlex.
- Cancer associated fibroblasts: heterogenous modifiers of treatment response.Translational cancer research · 2026Article
- [Breast cancer research : BCR · 2026Article
- AOH1996, an Inhibitor of PCNA, Sensitises Breast Cancer Cells to Cytotoxic Chemotherapy.Breast cancer (Dove Medical Press) · 2026Article
- Crosstalk between heterogeneous cancer-associated fibroblast subpopulations and the immune system in breast cancer: key players and promising therapeutic targets.Journal of experimental & clinical cancer research : CR · 2025Review
- Bridging the tumor microenvironment: the pivotal role of cancer-associated fibroblasts in tumor cachexia development.Molecular cancer · 2025Review
- Comparison of the procoagulant activity between extracellular vesicles obtained from cellular monolayers and spheroids.Journal of thrombosis and thrombolysis · 2025Article
- The role of CAFs in therapeutic resistance in triple negative breast cancer: an emerging challenge.Frontiers in molecular biosciences · 2025Review
- Article
- PRMT1 Sustains De Novo Fatty Acid Synthesis by Methylating PHGDH to Drive Chemoresistance in Triple-Negative Breast Cancer.Cancer research · 2024Article
- Article
- Studying luminal A and B subtypes of breast cancer under paracrine secretion of fibro-blasts.BioImpacts : BI · 2024Article
- Crosstalk and plasticity driving between cancer-associated fibroblasts and tumor microenvironment: significance of breast cancer metastasis.Journal of translational medicine · 2023Review
- Advances in immunotherapy for triple-negative breast cancer.Molecular cancer · 2023Review
- Cancer associated fibroblast derived gene signature determines cancer subtypes and prognostic model construction in head and neck squamous cell carcinomas.Cancer medicine · 2023Article
- NF-YAl drives EMT in ClaudinCell death & disease · 2023Article
- Mesothelioma-associated fibroblasts enhance proliferation and migration of pleural mesothelioma cells via c-Met/PI3K and WNT signaling but do not protect against cisplatin.Journal of experimental & clinical cancer research : CR · 2023Article
- The role of cancer-associated fibroblasts in breast cancer metastasis.Frontiers in oncology · 2023Review
- Cancer-associated fibroblasts: The chief architect in the tumor microenvironment.Frontiers in cell and developmental biology · 2023Review
- Potential Nanotechnology-Based Therapeutics to Prevent Cancer Progression through TME Cell-Driven Populations.Pharmaceutics · 2022Review
- Type I interferon-mediated tumor immunity and its role in immunotherapy.Cellular and molecular life sciences : CMLS · 2022Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTriple negative breast cancers (TNBC) have poor prognoses despite aggressive treatment with cytotoxic chemotherapy. Cancer-associated fibroblasts (CAFs) are prominent in tumour stroma. Our hypothesis was that CAFs modulate chemotherapy sensitivity.
methodsTNBC cells and breast fibroblasts were cultured; survival after chemotherapeutics was assessed using luciferase or clonogenic assays. Signalling was investigated using transcriptomics, reporters, recombinant proteins and blocking antibodies. Clinical relevance was investigated using immunohistochemistry.
resultsBreast CAFs dose-dependently protected TNBC cell lines MDA-MB-231 and MDA-MB-157, but not MDA-MB-468s, from chemotherapy. CAF-induced protection was associated with interferon (IFN) activation. CAFs were induced to express IFNβ1 by chemotherapy and TNBC co-culture, leading to paracrine activation in cancer cells. Recombinant IFNs were sufficient to protect MDA-MB-231 and MDA-MB-157 but not MDA-MB-468 cells. In TNBC patients, IFNβ1 expression in CAFs correlated with cancer cell expression of MX1, a marker of activated IFN signalling. High expression of IFNβ1 (CAFs) or MX1 (tumour cells) correlated with reduced survival after chemotherapy, especially in claudin-low tumours (which MDA-MB-231 and MDA-MB-157 cells represent). Antibodies that block IFN receptors reduced CAF-dependent chemoprotection.
conclusionsCAF-induced activation of IFN signalling in claudin-low TNBCs results in chemoresistance. Inhibition of this pathway represents a novel method to improve breast cancer outcomes.
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