ArticleCancer research2013
c-Src modulates estrogen-induced stress and apoptosis in estrogen-deprived breast cancer cells.
Article in Cancer research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.
- The potential mechanisms underlying phthalate-induced hypospadias: a systematic review of rodent model studies.Frontiers in endocrinology · 2024Pooled it
- BHBA attenuates endoplasmic reticulum stress-dependent neuroinflammation via the gut-brain axis in a mouse model of heat stress.CNS neuroscience & therapeutics · 2024Article
- Revisiting Estrogen for the Treatment of Endocrine-Resistant Breast Cancer: Novel Therapeutic Approaches.Cancers · 2023Review
- SRC kinase-mediated signaling pathways and targeted therapies in breast cancer.Breast cancer research : BCR · 2022Review
- Evolution of 3-(4-hydroxyphenyl)indoline-2-one as a scaffold for potent and selective anticancer activity.RSC medicinal chemistry · 2022Review
- Estrogen Receptor and the Unfolded Protein Response: Double-Edged Swords in Therapy for Estrogen Receptor-Positive Breast Cancer.Targeted oncology · 2022Review
- PERK, Beyond an Unfolded Protein Response Sensor in Estrogen-Induced Apoptosis in Endocrine-Resistant Breast Cancer.Molecular cancer research : MCR · 2022Review
- Estrogen Receptors-Mediated Apoptosis in Hormone-Dependent Cancers.International journal of molecular sciences · 2022Review
- Estrogen Receptor Complex to Trigger or Delay Estrogen-Induced Apoptosis in Long-Term Estrogen Deprived Breast Cancer.Frontiers in endocrinology · 2022Review
- Article
- Rapid Induction of the Unfolded Protein Response and Apoptosis by Estrogen Mimic TTC-352 for the Treatment of Endocrine-Resistant Breast Cancer.Molecular cancer therapeutics · 2021Article
- Network Pharmacology Integrated with Molecular Docking Explores the Mechanisms of Naringin against Osteoporotic Fracture by Regulating Oxidative Stress.Evidence-based complementary and alternative medicine : eCAM · 2021Article
- Screening for Combination Cancer Therapies With Dynamic Fuzzy Modeling and Multi-Objective Optimization.Frontiers in genetics · 2021Article
- Estrogen-induced epigenetic silencing ofEpigenetics · 2020Article
- Src couples estrogen receptor to the anticipatory unfolded protein response and regulates cancer cell fate under stress.Biochimica et biophysica acta. Molecular cell research · 2020Article
- Pharmacology and Molecular Mechanisms of Clinically Relevant Estrogen Estetrol and Estrogen Mimic BMI-135 for the Treatment of Endocrine-Resistant Breast Cancer.Molecular pharmacology · 2020Article
- Regulation of KLF4 by posttranslational modification circuitry in endocrine resistance.Cellular signalling · 2020Article
- Estrogen Signaling Induces Mitochondrial Dysfunction-Associated Autophagy and Senescence in Breast Cancer Cells.Biology · 2020Article
- Host Src controls gallid alpha herpesvirus 1 intercellular spread in a cellular fatty acid metabolism-dependent manner.Virology · 2019Article
- Suppression of Nuclear Factor-κB by Glucocorticoid Receptor Blocks Estrogen-Induced Apoptosis in Estrogen-Deprived Breast Cancer Cells.Molecular cancer therapeutics · 2019Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
The emergence of anti-estrogen resistance in breast cancer is an important clinical phenomenon affecting long-term survival in this disease. Identifying factors that convey cell survival in this setting may guide improvements in treatment. Estrogen (E2) can induce apoptosis in breast cancer cells that have been selected for survival after E2 deprivation for long periods (MCF-7:5C cells), but the mechanisms underlying E2-induced stress in this setting have not been elucidated. Here, we report that the c-Src kinase functions as a key adapter protein for the estrogen receptor (ER, ESR1) in its activation of stress responses induced by E2 in MCF-7:5C cells. E2 elevated phosphorylation of c-Src, which was blocked by 4-hydroxytamoxifen (4-OHT), suggesting that E2 activated c-Src through the ER. We found that E2 activated the sensors of the unfolded protein response (UPR), IRE1α (ERN1) and PERK kinase (EIF2AK3), the latter of which phosphorylates eukaryotic translation initiation factor-2α (eIF2α). E2 also dramatically increased reactive oxygen species production and upregulated expression of heme oxygenase HO-1 (HMOX1), an indicator of oxidative stress, along with the central energy sensor kinase AMPK (PRKAA2). Pharmacologic or RNA interference-mediated inhibition of c-Src abolished the phosphorylation of eIF2α and AMPK, blocked E2-induced ROS production, and inhibited E2-induced apoptosis. Together, our results establish that c-Src kinase mediates stresses generated by E2 in long-term E2-deprived cells that trigger apoptosis. This work offers a mechanistic rationale for a new approach in the treatment of endocrine-resistant breast cancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.