ArticleOncotarget2015
Stromal cells promote anti-estrogen resistance of breast cancer cells through an insulin-like growth factor binding protein 5 (IGFBP5)/B-cell leukemia/lymphoma 3 (Bcl-3) axis.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 47 citations in OpenAlex.
- Extracellular Vesicles Secreted by Cancer-Associated Fibroblasts Drive Non-Invasive Cancer Cell Progression to Metastasis via TGF-β Signalling Hyperactivation.Journal of extracellular vesicles · 2025Article
- Targeting Glycolysis for Treatment of Breast Cancer Resistance: Current Progress and Future Prospects.International journal of biological sciences · 2025Review
- The SEMA3F-NRP1/NRP2 axis is a key factor in the acquisition of invasive traits in in situ breast ductal carcinoma.Breast cancer research : BCR · 2024Article
- The complex nature of heterogeneity and its roles in breast cancer biology and therapeutic responsiveness.Frontiers in endocrinology · 2023Review
- A CAF-Fueled TIMP-1/CD63/ITGB1/STAT3 Feedback Loop Promotes Migration and Growth of Breast Cancer Cells.Cancers · 2022Article
- BCL3 expression is strongly associated with the occurrence of breast cancer relapse under tamoxifen treatment in a retrospective cohort study.Virchows Archiv : an international journal of pathology · 2022Article
- Insulin-like growth factor binding protein 5: Diverse roles in cancer.Frontiers in oncology · 2022Review
- Biological effects and regulation of IGFBP5 in breast cancer.Frontiers in endocrinology · 2022Review
- Review
- The Relationship Between Mesenchymal Stem Cells and Tumor Dormancy.Frontiers in cell and developmental biology · 2021Review
- Identification of Four Genes as Prognosis Signatures in Lung Adenocarcinoma Microenvironment.Pharmacogenomics and personalized medicine · 2021Article
- Nuclear Mechanisms Involved in Endocrine Resistance.Frontiers in oncology · 2021Review
- Carcinoma-Associated Fibroblasts Promote Growth of Sox2-Expressing Breast Cancer Cells.Cancers · 2020Article
- Late effects of adjuvant chemotherapy adumbrate dormancy complexity in breast cancer.Breast (Edinburgh, Scotland) · 2020Article
- Protein‑ and growth‑modulatory effects of carcinoma‑associated fibroblasts on breast cancer cells: Role of interleukin‑6.International journal of oncology · 2020Article
- Twiner: correlation-based regularization for identifying common cancer gene signatures.BMC bioinformatics · 2019Article
- Mutual concessions and compromises between stromal cells and cancer cells: driving tumor development and drug resistance.Cellular oncology (Dordrecht, Netherlands) · 2018Review
- Long-term exposure to carcinoma-associated fibroblasts makes breast cancer cells addictive to integrin β1.Oncotarget · 2018Article
- Article
- Jujube leaf green tea extracts inhibits hepatocellular carcinoma cells by activating AMPK.Oncotarget · 2017Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
There is strong evidence that stromal cells promote drug resistance of cancer. Here, we show that mesenchymal stem cells (MSCs) and carcinoma-associated fibroblasts (CAFs) desensitize ERα-positive breast cancer cells to the anti-estrogen fulvestrant. In search for the mechanism, we found that MSCs and CAFs similarly increased the activity of the PI3K/AKT and the JAK/STAT3 pathways and upregulated the expression of integrin β1, IGF1R, HIF1α, CAIX and Bcl-3 in MCF-7 cells. Further analyses revealed that MSCs and CAFs coordinately induce these changes by triggering the downregulation of IGFBP5. Loss of IGFBP5 in MCF-7 cells was an early and long-lasting event in response to MSCs and CAFs and was accompanied by growth stimulation both in the absence and presence of fulvestrant. The growth-stimulatory effect in the absence of fulvestrant could be attributed to PI3K/AKT pathway activation and could be mimicked by insulin. The growth-promoting effect in the presence of fulvestrant depended upon the upregulation of Bcl-3. By cRNA microarray analysis we identified additional IGFBP5 targets, of which two (KLHL4 and SEPP1) were inversely regulated by IGFBP5 and Bcl-3. BT474 cells also responded to stromal cells by downregulating IGFBP5 and upregulating the P-AKT, Bcl-3 and IGF1R levels, whereas T47D cells did not show any of these responses. In conclusion, our data suggest that, by targeting IGFBP5 expression in ERα-positive breast cancer cells, such as MCF-7 cells, MSCs and CAFs are able to orchestrate a variety of events, particularly activation of the PI3K/AKT pathway, upregulation of Bcl-3 expression and desensitization to anti-estrogen.
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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.