ArticlePLoS genetics2017
SNPs near the cysteine proteinase cathepsin O gene (CTSO) determine tamoxifen sensitivity in ERα-positive breast cancer through regulation of BRCA1.
Article in PLoS genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- Interaction Between SNP Genotype and Efficacy of Anastrozole and Exemestane in Early-Stage Breast Cancer.Clinical pharmacology and therapeutics · 2021Trial
- Article
- Cathepsins and Skin Cancer (Malignant Melanoma, Basal Cell Carcinoma, and Squamous Cell Carcinoma): Insight From Genetic Correlation and Mendelian Randomization.Clinical, cosmetic and investigational dermatology · 2025Article
- The multifaceted roles of cathepsins in immune and inflammatory responses: implications for cancer therapy, autoimmune diseases, and infectious diseases.Biomarker research · 2024Review
- Causal relationship between cathepsins and major salivary gland neoplasms: a bidirectional Mendelian randomization study.Gland surgery · 2024Article
- Reduced expression of cathepsin F predicts poor prognosis in patients with clear cell renal cell carcinoma.Scientific reports · 2024Article
- Cathepsins and cancer risk: a Mendelian randomization study.Frontiers in endocrinology · 2024Article
- Preclinical-to-clinical Anti-cancer Drug Response Prediction and Biomarker Identification Using TINDL.Genomics, proteomics & bioinformatics · 2023Article
- Cysteine Cathepsins in Breast Cancer: Promising Targets for Fluorescence-Guided Surgery.Molecular imaging and biology · 2023Review
- Cathepsins in oral diseases: mechanisms and therapeutic implications.Frontiers in immunology · 2023Review
- Combinatorial Power of cfDNA, CTCs and EVs in Oncology.Diagnostics (Basel, Switzerland) · 2022Review
- Glycosylated Cathepsin V Serves as a Prognostic Marker in Lung Cancer.Frontiers in oncology · 2022Article
- Prolactin and endocrine therapy resistance in breast cancer: The next potential hope for breast cancer treatment.Journal of cellular and molecular medicine · 2021Review
- Functional genomics based on germline genome-wide association studies of endocrine therapy for breast cancer.Pharmacogenomics · 2020Article
- Integrative genomic analysis identifies associations of molecular alterations to APOBEC and BRCA1/2 mutational signatures in breast cancer.Molecular genetics & genomic medicine · 2019Article
- Identification of Crucial Candidate Genes and Pathways in Glioblastoma Multiform by Bioinformatics Analysis.Biomolecules · 2019Article
- The lncRNA MIR2052HG regulates ERα levels and aromatase inhibitor resistance through LMTK3 by recruiting EGR1.Breast cancer research : BCR · 2019Article
- ZNF423: A New Player in Estrogen Receptor-Positive Breast Cancer.Frontiers in endocrinology · 2018Review
- The Multifaceted Role of the Lysosomal Protease Cathepsins in Kidney Disease.Frontiers in cell and developmental biology · 2017Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Tamoxifen is one of the most commonly employed endocrine therapies for patients with estrogen receptor α (ERα)-positive breast cancer. Unfortunately the clinical benefit is limited due to intrinsic and acquired drug resistance. We previously reported a genome-wide association study that identified common SNPs near the CTSO gene and in ZNF423 associated with development of breast cancer during tamoxifen therapy in the NSABP P-1 and P-2 breast cancer prevention trials. Here, we have investigated their roles in ERα-positive breast cancer growth and tamoxifen response, focusing on the mechanism of CTSO. We performed in vitro studies including luciferase assays, cell proliferation, and mass spectrometry-based assays using ERα-positive breast cancer cells and a panel of genomic data-rich lymphoblastoid cell lines. We report that CTSO reduces the protein levels of BRCA1 and ZNF423 through cysteine proteinase-mediated degradation. We also have identified a series of transcription factors of BRCA1 that are regulated by CTSO at the protein level. Importantly, the variant CTSO SNP genotypes are associated with increased CTSO and decreased BRCA1 protein levels that confer resistance to tamoxifen. Characterization of the effect of both CTSO SNPs and ZNF423 SNPs on tamoxifen response revealed that cells with different combinations of CTSO and ZNF423 genotypes respond differently to Tamoxifen, PARP inhibitors or the combination of the two drugs due to SNP dependent differential regulation of BRCA1 levels. Therefore, these genotypes might be biomarkers for selection of individual drug to achieve the best efficacy.
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