ArticleBMC cancer2013
The Wnt signalling pathway is upregulated in an in vitro model of acquired tamoxifen resistant breast cancer.
Article in BMC cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed.
- Baseline gene expression and dynamic endocrine therapy use in ER+ breast cancer: associations with recurrence in a real-world cohort.Research square · 2026Article
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- The impact of the telomerase inhibitor on the Wnt signaling pathway in breast cancer and breast cancer stem cells.Molecular biology reports · 2026Article
- Recent Advances (2020-2025) in Estrogen and ER-Positive Breast Cancer: Receptor Signaling, Tumor Microenvironment, Endocrine Therapy Resistance and Innovative Treatment Strategies-A Comprehensive Review.Cancer management and research · 2026Review
- Exploring the Therapeutic Potential ofAnti-cancer agents in medicinal chemistry · 2026Review
- LEM4 interacts with β-catenin and promotes β-catenin-dependent transcription activity to confers ribociclib resistance in breast cancer cells.Scientific reports · 2025Article
- Inhibition of Wnt/β-catenin increases anti-tumor activity by synergizing with sorafenib in hepatocellular carcinoma.Cell death & disease · 2025Article
- Hi-C profiling in tissues reveals 3D chromatin-regulated breast tumor heterogeneity informing a looping-mediated therapeutic avenue.Cell reports · 2025Article
- Identification of a TNIK-CDK9 Axis as a Targetable Strategy for Platinum-Resistant Ovarian Cancer.Molecular cancer therapeutics · 2025Article
- Role of EMT in drug resistance of breast cancer: molecular mechanisms and therapeutic strategies.Frontiers in oncology · 2025Review
- Ivermectin inhibits epithelial-to-mesenchymal transition via Wnt signaling in endocrine-resistant breast cancer cells.PloS one · 2025Article
- Article
- A Putative Frizzled 7-Targeting Compound Acts as a Firefly Luciferase Inhibitor.Journal of medicinal chemistry · 2024Article
- Dexamethasone-tamoxifen combination exerts synergistic therapeutic effects in tamoxifen-resistance breast cancer cells.Bioscience reports · 2024Article
- Wnt signaling and tumors (Review).Molecular and clinical oncology · 2024Review
- Glutamine synthetase regulates the immune microenvironment and cancer development through the inflammatory pathway.International journal of medical sciences · 2023Article
- The role of the tumor microenvironment in endocrine therapy resistance in hormone receptor-positive breast cancer.Frontiers in endocrinology · 2023Review
- FDXR drives primary and endocrine-resistant tumor cell growth in ER+ breast cancer via CPT1A-mediated fatty acid oxidation.Frontiers in oncology · 2023Article
- The landscape of exosomal non-coding RNAs in breast cancer drug resistance, focusing on underlying molecular mechanisms.Frontiers in pharmacology · 2023Review
- Article
20 more citing papers are in PubMed but not listed here.
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6 authors.
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Abstract
backgroundAcquired resistance to Tamoxifen remains a critical problem in breast cancer patient treatment, yet the underlying causes of resistance have not been fully elucidated. Abberations in the Wnt signalling pathway have been linked to many human cancers, including breast cancer, and appear to be associated with more metastatic and aggressive types of cancer. Here, our aim was to investigate if this key pathway was involved in acquired Tamoxifen resistance, and could be targeted therapeutically.
methodsAn in vitro model of acquired Tamoxifen resistance (named TamR) was generated by growing the estrogen receptor alpha (ER) positive MCF7 breast cancer cell line in increasing concentrations of Tamoxifen (up to 5 uM). Alterations in the Wnt signalling pathway and epithelial to mesenchymal transition (EMT) in response to Tamoxifen and treatment with the Wnt inhibitor, IWP-2 were measured via quantitative RT-PCR (qPCR) and TOP/FOP Wnt reporter assays. Resistance to Tamoxifen, and effects of IWP-2 treatment were determined by MTT proliferation assays.
resultsTamR cells exhibited increased Wnt signalling as measured via the TOP/FOP Wnt luciferase reporter assays. Genes associated with both the β-catenin dependent (AXIN2, MYC, CSNK1A1) and independent arms (ROR2, JUN), as well as general Wnt secretion (PORCN) of the Wnt signalling pathway were upregulated in the TamR cells compared to the parental MCF7 cell line. Treatment of the TamR cell line with human recombinant Wnt3a (rWnt3a) further increased the resistance of both MCF7 and TamR cells to the anti-proliferative effects of Tamoxifen treatment. TamR cells demonstrated increased expression of EMT markers (VIM, TWIST1, SNAI2) and decreased CDH1, which may contribute to their resistance to Tamoxifen. Treatment with the Wnt inhibitor, IWP-2 inhibited cell proliferation and markers of EMT.
conclusionsThese data support the role of the Wnt signalling pathway in acquired resistance to Tamoxifen. Further research into the mechanism by which activated Wnt signalling inhibits the effects of Tamoxifen should be undertaken. As a number of small molecules targeting the Wnt pathway are currently in pre-clinical development, combinatorial treatment with endocrine agents and Wnt pathway inhibitors may be a useful therapeutic option in the future for a subset of breast cancer patients.
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