ArticlePloS one2013
Fulvestrant-induced cell death and proteasomal degradation of estrogen receptor α protein in MCF-7 cells require the CSK c-Src tyrosine kinase.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 74 citations in OpenAlex.
- LYN-activating mutations mediate antiestrogen resistance in estrogen receptor-positive breast cancer.The Journal of clinical investigation · 2014Trial
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- CK8/18 and Claudin Profile of Female Breast Cancers from Botswana.Breast cancer : basic and clinical research · 2026Article
- Ivermectin inhibits ER, HER2, and TGF-β pathways in ER-positive and endocrine-resistant breast cancer cells.PloS one · 2026Article
- TOP2B modulates DNA supercoiling and chromatin contacts during transcriptional induction.Science advances · 2025Article
- The Effect of Bazedoxifene and Fulvestrant for Preventing Ovarian Hyperstimulation Syndrome: An Experimental Study.Journal of clinical medicine · 2025Article
- Estrogen-like Activity ofBiomedicines · 2025Article
- IL-6 predicts CDK4/6 inhibitor resistance, identifying STAT3 as a target in HR + /HER2-negative metastatic breast cancer.NPJ precision oncology · 2025Article
- Treating ER-positive breast cancer: a review of the current FDA-approved SERMs and SERDs and their mechanisms of action.Oncology reviews · 2025Review
- Topological regulation of the estrogen transcriptional response by ZATT-mediated inhibition of TOP2B activity.bioRxiv : the preprint server for biology · 2024Article
- Insulin-like growth factor-binding protein-3 is induced by tamoxifen and fulvestrant and modulates fulvestrant response in breast cancer cells.Frontiers in oncology · 2024Article
- Obesity-Senescence-Breast Cancer: Clinical Presentation of a Common Unfortunate Cycle.Advances in experimental medicine and biology · 2024Review
- Sex-specific outcomes in cancer therapy: the central role of hormones.Frontiers in medical technology · 2024Review
- Critical Roles of SRC-3 in the Development and Progression of Breast Cancer, Rendering It a Prospective Clinical Target.Cancers · 2023Review
- Article
- Biological Activity of Oleanolic Acid Derivatives HIMOXOL and Br-HIMOLID in Breast Cancer Cells Is Mediated by ER and EGFR.International journal of molecular sciences · 2023Article
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- CRISPR-Cas9-based genome-wide screening identified novel targets for treating sorafenib-resistant hepatocellular carcinoma: a cross-talk between FGF21 and the NRF2 pathway.Science China. Life sciences · 2022Article
- Prolonged estrogen deprivation triggers a broad immunosuppressive phenotype in breast cancer cells.Molecular oncology · 2022Article
- Regulation of aromatase in cancer.Molecular and cellular biochemistry · 2021Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fulvestrant is a representative pure antiestrogen and a Selective Estrogen Receptor Down-regulator (SERD). In contrast to the Selective Estrogen Receptor Modulators (SERMs) such as 4-hydroxytamoxifen that bind to estrogen receptor α (ERα) as antagonists or partial agonists, fulvestrant causes proteasomal degradation of ERα protein, shutting down the estrogen signaling to induce proliferation arrest and apoptosis of estrogen-dependent breast cancer cells. We performed genome-wide RNAi knockdown screenings for protein kinases required for fulvestrant-induced apoptosis of the MCF-7 estrogen-dependent human breast caner cells and identified the c-Src tyrosine kinase (CSK), a negative regulator of the oncoprotein c-Src and related protein tyrosine kinases, as one of the necessary molecules. Whereas RNAi knockdown of CSK in MCF-7 cells by shRNA-expressing lentiviruses strongly suppressed fulvestrant-induced cell death, CSK knockdown did not affect cytocidal actions of 4-hydroxytamoxifen or paclitaxel, a chemotherapeutic agent. In the absence of CSK, fulvestrant-induced proteasomal degradation of ERα protein was suppressed in both MCF-7 and T47D estrogen-dependent breast cancer cells whereas the TP53-mutated T47D cells were resistant to the cytocidal action of fulvestrant in the presence or absence of CSK. MCF-7 cell sensitivities to fulvestrant-induced cell death or ERα protein degradation was not affected by small-molecular-weight inhibitors of the tyrosine kinase activity of c-Src, suggesting possible involvement of other signaling molecules in CSK-dependent MCF-7 cell death induced by fulvestrant. Our observations suggest the importance of CSK in the determination of cellular sensitivity to the cytocidal action of fulvestrant.
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