ArticleProceedings of the National Academy of Sciences of the United States of America2011
High-throughput ectopic expression screen for tamoxifen resistance identifies an atypical kinase that blocks autophagy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed.
- FAK signaling pathways are modulated by HSPB8 and BAG3 in breast cancer.Cell communication and signaling : CCS · 2026Article
- Development of a polygenic score predicting drug resistance and patient outcome in breast cancer.NPJ precision oncology · 2024Article
- The ischemia-enhanced myocardial infarction protection-related lncRNA protects against acute myocardial infarction.MedComm · 2024Article
- The Multifaceted Functions of Prion Protein (PrPCancers · 2023Review
- LINC01116 affects patient survival differently and is dissimilarly expressed in ER+ and ER- breast cancer samples.Cancer reports (Hoboken, N.J.) · 2023Article
- Review
- GDNF-RET signaling and EGR1 form a positive feedback loop that promotes tamoxifen resistance via cyclin D1.BMC cancer · 2023Article
- ESR1 mutant breast cancers show elevated basal cytokeratins and immune activation.Nature communications · 2022Article
- Oestrogen Receptor Isoforms May Represent a Therapeutic Target in Oesophageal Adenocarcinoma.Cancers · 2022Article
- The role of lncRNA H19 in tumorigenesis and drug resistance of human Cancers.Frontiers in genetics · 2022Review
- Endocrine resistance in breast cancer: from molecular mechanisms to therapeutic strategies.Journal of molecular medicine (Berlin, Germany) · 2021Review
- A mechanistic model captures the emergence and implications of non-genetic heterogeneity and reversible drug resistance in ER+ breast cancer cells.NAR cancer · 2021Article
- The multifaceted role of lemur tyrosine kinase 3 in health and disease.Open biology · 2021Review
- Hyperleptinemia in obese state renders luminal breast cancers refractory to tamoxifen by coordinating a crosstalk between Med1, miR205 and ErbB.NPJ breast cancer · 2021Article
- The Role of HSPB8, a Component of the Chaperone-Assisted Selective Autophagy Machinery, in Cancer.Cells · 2021Review
- Identification of Key lncRNA-mRNA Pairs and Functional lncRNAs in Breast Cancer by Integrative Analysis of TCGA Data.Frontiers in genetics · 2021Article
- Autophagy as a mechanism for anti-angiogenic therapy resistance.Seminars in cancer biology · 2020Review
- Although c‑MYC contributes to tamoxifen resistance, it improves cisplatin sensitivity in ER‑positive breast cancer.International journal of oncology · 2020Article
- Identification of Tamoxifen-Resistant Breast Cancer Cell Lines and Drug Response Signature.Frontiers in molecular biosciences · 2020Article
- Competing Endogenous RNA (ceRNA) Network Analysis of Autophagy-Related Genes in Hepatocellular Carcinoma.Pharmacogenomics and personalized medicine · 2020Article
5 more citing papers are in PubMed but not listed here.
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10 authors.
Funding
Abstract
Resistance to tamoxifen in breast cancer patients is a serious therapeutic problem and major efforts are underway to understand underlying mechanisms. Resistance can be either intrinsic or acquired. We derived a series of subcloned MCF7 cell lines that were either highly sensitive or naturally resistant to tamoxifen and studied the factors that lead to drug resistance. Gene-expression studies revealed a signature of 67 genes that differentially respond to tamoxifen in sensitive vs. resistant subclones, which also predicts disease-free survival in tamoxifen-treated patients. High-throughput cell-based screens, in which >500 human kinases were independently ectopically expressed, identified 31 kinases that conferred drug resistance on sensitive cells. One of these, HSPB8, was also in the expression signature and, by itself, predicted poor clinical outcome in one cohort of patients. Further studies revealed that HSPB8 protected MCF7 cells from tamoxifen and blocked autophagy. Moreover, silencing HSBP8 induced autophagy and caused cell death. Tamoxifen itself induced autophagy in sensitive cells but not in resistant ones, and tamoxifen-resistant cells were sensitive to the induction of autophagy by other drugs. These results may point to an important role for autophagy in the sensitivity to tamoxifen.
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