ArticleOncogene2015
A kinase inhibitor screen identifies Mcl-1 and Aurora kinase A as novel treatment targets in antiestrogen-resistant breast cancer cells.
Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 54 citations in OpenAlex.
- Evaluation of Alisertib Alone or Combined With Fulvestrant in Patients With Endocrine-Resistant Advanced Breast Cancer: The Phase 2 TBCRC041 Randomized Clinical Trial.JAMA oncology · 2023Trial
- FGFR1 Suppresses STING-Mediated Interferon Response in Endocrine Therapy-Resistant Breast Cancer.Cancer research communications · 2026Article
- Seize the engine: Emerging cell cycle targets in breast cancer.Clinical and translational medicine · 2024Review
- Emerging systemic therapy options beyond CDK4/6 inhibitors for hormone receptor-positive HER2-negative advanced breast cancer.NPJ breast cancer · 2023Review
- Targeting MCL-1 protein to treat cancer: opportunities and challenges.Frontiers in oncology · 2023Review
- Understanding MCL1: from cellular function and regulation to pharmacological inhibition.The FEBS journal · 2022Review
- MCL-1 is a clinically targetable vulnerability in breast cancer.Cell cycle (Georgetown, Tex.) · 2022Review
- Tamoxifen resistance-related ceRNA network for breast cancer.Frontiers in cell and developmental biology · 2022Article
- HAS2-Ezrin-ER axis plays a role in acquired antiestrogen resistance of ER-positive breast cancer.Frontiers in pharmacology · 2022Article
- Molecular markers associated with the outcome of tamoxifen treatment in estrogen receptor-positive breast cancer patients: scoping review and in silico analysis.Discover oncology · 2021Article
- Differential reprogramming of breast cancer subtypes in 3D cultures and implications for sensitivity to targeted therapy.Scientific reports · 2021Article
- MCM3 upregulation confers endocrine resistance in breast cancer and is a predictive marker of diminished tamoxifen benefit.NPJ breast cancer · 2021Article
- Aurora A and Mcl-1: new potential treatment targets in antiestrogen-resistant breast cancer.Molecular & cellular oncology · 2021Article
- Identification of Ten Mitosis Genes Associated with Tamoxifen Resistance in Breast Cancer.OncoTargets and therapy · 2021Article
- Increased Expression of Gankyrin and Stemness Factor Oct-4 are Associated with Unfavorable Clinical Outcomes and Poor Benefit of Tamoxifen in Breast Carcinoma Patients.Pathology oncology research : POR · 2020Article
- Smart drug combinations for cervical cancer: dual targeting of Bcl-2 family of proteins and aurora kinases.American journal of cancer research · 2020Article
- The miR-186-3p/EREG axis orchestrates tamoxifen resistance and aerobic glycolysis in breast cancer cells.Oncogene · 2019Article
- WP1130 reveals USP24 as a novel target in T-cell acute lymphoblastic leukemia.Cancer cell international · 2019Article
- Article
- Phase I trial to evaluate the addition of alisertib to fulvestrant in women with endocrine-resistant, ER+ metastatic breast cancer.Breast cancer research and treatment · 2018Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Antiestrogen resistance is a major problem in breast cancer treatment. Therefore, the search for new therapeutic targets and biomarkers for antiestrogen resistance is crucial. In this study, we performed a kinase inhibitor screen on antiestrogen responsive MCF-7 cells and a panel of MCF-7-derived tamoxifen- and fulvestrant-resistant cell lines. Our focus was to identify common and distinct molecular mechanisms involved in tamoxifen- and fulvestrant-resistant cell growth. We identified 18 inhibitors, of which the majority was common for both tamoxifen- and fulvestrant-resistant cell lines. Two compounds, WP1130 and JNJ-7706621, exhibiting prominent preferential growth inhibition of antiestrogen-resistant cell lines, were selected for further studies. WP1130, a deubiquitinase inhibitor, induced caspase-mediated cell death in both tamoxifen- and fulvestrant-resistant cell lines by destabilization of the anti-apoptotic protein Mcl-1. Mcl-1 expression was found upregulated in the antiestrogen-resistant cell lines and depletion of Mcl-1 in resistant cells caused decreased viability. JNJ-7706621, a dual Aurora kinase and cyclin-dependent kinase inhibitor, specifically inhibited growth and caused G2 phase cell cycle arrest of the tamoxifen-resistant cell lines. Knockdown studies showed that Aurora kinase A is essential for growth of the tamoxifen-resistant cells and inhibition of Aurora kinase A resensitized tamoxifen-resistant cells to tamoxifen treatment. Preferential growth inhibition by WP1130 and JNJ-7706621 was also found in T47D-derived tamoxifen-resistant cell lines, pointing at Mcl-1 and Aurora kinase A as potential treatment targets. In addition, tumor samples from 244 estrogen receptor-positive breast cancer patients treated with adjuvant tamoxifen showed that higher expression level of Aurora kinase A was significantly associated with shorter disease-free and overall survival, demonstrating the potential of Aurora kinase A as a biomarker for tamoxifen resistance.
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