ArticleOncoTargets and therapy2020
SRC Promotes Tamoxifen Resistance in Breast Cancer via Up-Regulating SIRT1.
Article in OncoTargets and therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 16 citations in OpenAlex.
- SIRT1 Promotes Breast Cancer Stem Cell-Associated Properties and Represents a Potential Therapeutic Target.International journal of molecular sciences · 2026Article
- Targeting SRC enhances differentiation and promotes multifaceted cell death mechanisms in recurrent group 3 medulloblastoma.Cell death & disease · 2026Article
- All the Way: A Decade of SIRT1 in Breast Cancer.Biomedicines · 2026Review
- Review
- Radiogenomic Landscape of Metastatic Endocrine-Positive Breast Cancer Resistant to Aromatase Inhibitors.Cancers · 2025Review
- Crosstalk of methylation and tamoxifen in breast cancer (Review).Molecular medicine reports · 2024Review
- Pan-cancer analysis of super-enhancer-induced LINC00862 and validation as a SIRT1-promoting factor in cervical cancer and gastric cancer.Translational oncology · 2024Article
- Comprehensive Transcriptomic and Proteomic Analyses Identify a Candidate Gene Set in Cross-Resistance for Endocrine Therapy in Breast Cancer.International journal of molecular sciences · 2022Article
- The prognostic implications of SIRTs expression in breast cancer: a systematic review and meta-analysis.Discover oncology · 2022Article
- Kinase activity profiling in renal cell carcinoma, benign renal tissue and in response to four different tyrosine kinase inhibitors.Oncotarget · 2022Article
- ESR1 fusions and therapeutic resistance in metastatic breast cancer.Frontiers in oncology · 2022Review
- Molecular Mechanisms of Endocrine Resistance in Estrogen-Positive Breast Cancer.Frontiers in endocrinology · 2021Review
- The Utility of SOX2 and AGR2 Biomarkers as Early Predictors of Tamoxifen Resistance in ER-Positive Breast Cancer Patients.International journal of surgical oncology · 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
backgroundEndocrine therapy plays a key role in estrogen receptor-positive breast cancer patients; but, tamoxifen resistance could be a real difficulty for these patients. Several attempts have been made to explore the mechanism and new therapies for these patients. We intend to clarify the expression change of SRC and SIRT1 in tamoxifen-resistant breast cancer cells and explore their functions on tamoxifen resistance.
methodsSRC and SIRT1 expressions were analyzed by RNA sequencing, qPCR and Western blotting. Loss and gain of function of SRC and SIRT1 were utilized to indicate their oncogenic roles in tamoxifen resistance in vitro and in vivo. Kaplan-Meier analysis and receiver operating characteristic curve were used to evaluate the survival and the predicted effects of SRC and SIRT1 on patients' prognosis.
resultsHigh expressions of SRC and/or SIRT1 were found in tamoxifen-resistant cells and related to poor overall survival (p<0.05 for SRC, p<0.001 for SIRT1, p<0.001 for SRC and SIRT1) and cancer-specific survival (p<0.05 for SRC, p<0.01 for SIRT1, p<0.01 for SRC and SIRT1) of tamoxifen-treated breast cancer patients. Down-regulation of SRC (p<0.01) or SIRT1 (p<0.05) separately reversed the resistance to tamoxifen and the minimal concentration of SRC inhibitor KX-01 (p<0.05) or SIRT1 inhibitor EX527 (p<0.001) could also suppress cell proliferation. The expression level of SIRT1 was positively correlated with that of SRC. Overexpression of SRC significantly promotes the cell resistance to tamoxifen inhibited by SIRT1 (p<0.01). In vivo experiments confirmed the effects of SRC on tumor growth by over- or down-regulating SRC expression (p<0.001 and p<0.001, respectively).
conclusionSRC and SIRT1 are both up-regulated in tamoxifen-resistant breast cancer cells and related to a poor prognosis in tamoxifen-treated breast cancer. Moreover, SRC could promote tamoxifen resistance by up-regulating SIRT1. SRC and SIRT1 might be novel therapeutic targets in tamoxifen-resistant breast cancer and the interaction between SRC and SIRT1 needs to be further explored.
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