ArticleTranslational oncology2020
Downregulation of CXXC Finger Protein 4 Leads to a Tamoxifen-resistant Phenotype in Breast Cancer Cells Through Activation of the Wnt/β-catenin Pathway.
Article in Translational oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
- Molecular Mechanisms Underlying Recurrence in Triple-Positive Breast Cancer (ER+/PR+/HER2+) and Potential Repurposing of Multi-Target Inhibitors.International journal of molecular sciences · 2026Review
- Nanoparticle hydrogel system delivery of miR-494-3p to improve tendon healing by targeting CXXC4.Gene therapy · 2026Article
- Integrated analysis of differential intra-chromosomal community interactions: A study of breast cancer.Artificial intelligence in medicine · 2025Article
- Role of circular RNAs in preeclampsia (Review).Experimental and therapeutic medicine · 2024Review
- Tamoxifen resistance induction results in the upregulation of ABCG2 expression and mitoxantrone resistance in MCF-7 breast cancer cells.Naunyn-Schmiedeberg's archives of pharmacology · 2023Article
- Article
- Relationship of micro-RNA, mRNA and eIF Expression in Tamoxifen-Adapted MCF-7 Breast Cancer Cells: Impact of miR-1972 on Gene Expression, Proliferation and Migration.Biomolecules · 2022Article
- Lemur tyrosine kinase 2 silencing inhibits the proliferation of gastric cancer cells by regulating GSK-3β phosphorylation and β-catenin nuclear translocation.Bioengineered · 2022Article
- A novel lncRNA derived from an ultraconserved region: lnc-RNA biology · 2021Article
- Utilizing the Hippo pathway as a therapeutic target for combating endocrine-resistant breast cancer.Cancer cell international · 2021Review
- High-Throughput Screening of Mouse Gene Knockouts Identifies Established and Novel High Body Fat Phenotypes.Diabetes, metabolic syndrome and obesity : targets and therapy · 2021Article
- Paeoniflorin Sensitizes Breast Cancer Cells to Tamoxifen by Downregulating microRNA-15b via the FOXO1/CCND1/β-Catenin Axis.Drug design, development and therapy · 2021Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tamoxifen is a successful endocrine therapy drug for estrogen receptor-positive (ER+) breast cancer. However, resistance to tamoxifen compromises the efficacy of endocrine treatment. In the present study, we identified potential tamoxifen resistance-related gene markers and investigated their mechanistic details. First, we established two ER + breast cancer cell lines resistant to tamoxifen, named MCF-7/TMR and BT474/TMR. Gene expression profiling showed that CXXC finger protein 4 (CXXC4) expression is lower in MCF-7/TMR cells than in MCF-7 cells. Furthermore, CXXC4 mRNA and protein expression are lower in the resistant cell lines than in the corresponding parental cell lines. We also investigated the correlation between CXXC4 and endocrine resistance in ER + breast cancer cells. CXXC4 knockdown accelerates cell proliferation in vitro and in vivo and renders breast cancer cells insensitive to tamoxifen, whereas CXXC4 overexpression inhibits cancer cell growth and increases tamoxifen sensitivity of resistant cells. In addition, we demonstrated that CXXC4 inhibits Wnt/β-catenin signaling in cancer cells by modulating the phosphorylation of GSK-3β, influencing the integrity of the β-catenin degradation complex. Silencing the CXXC4 gene upregulates expression of cyclinD1 and c-myc (the downstream targets of Wnt signaling) and promotes cell cycle progression. Conversely, ectopic expression of CXXC4 downregulates the expression of these proteins and arrests the cell cycle in the G0/G1 phase. Finally, the small-molecule inhibitor XAV939 suppresses Wnt signaling and sensitizes resistant cells to tamoxifen. These results indicate that components of Wnt pathway that are early in response to tamoxifen could be involved as an intrinsic factor of the transition to endocrine resistance, and inhibition of Wnt signaling may be an effective therapeutic strategy to overcome tamoxifen resistance.
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