ArticleBreast cancer research : BCR2012
Targeting the PELP1-KDM1 axis as a potential therapeutic strategy for breast cancer.
Article in Breast cancer research : BCR, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 81 citations in OpenAlex.
- Nucleic sexual hormone receptor signaling pathways in breast cancer: function regulation, crosstalk, and therapeutic implications.NPJ precision oncology · 2026Review
- Histone lysine demethylases in breast cancer: molecular mechanisms, biological functions, and therapeutic intervention.Molecular cancer · 2025Review
- The PELP1 Pathway and Its Importance in Cancer Treatment.Biomolecules · 2025Review
- Lysine-specific demethylase 1 deletion reshapes tumour microenvironment to overcome acquired resistance to anti-programmed death 1 therapy in liver cancer.Clinical and translational medicine · 2025Article
- PELP1 Is a Novel Therapeutic Target in Hepatocellular Carcinoma.Cancer research communications · 2024Article
- The emerging roles of histone demethylases in cancers.Cancer metastasis reviews · 2024Review
- Targeting PELP1 oncogenic signaling in TNBC with the small molecule inhibitor SMIP34.Breast cancer research and treatment · 2023Article
- Targeting epigenetic regulators to overcome drug resistance in cancers.Signal transduction and targeted therapy · 2023Review
- Targeting the LSD1/KDM1 Family of Lysine Demethylases in Cancer and Other Human Diseases.Advances in experimental medicine and biology · 2023Review
- A First-in-Class Inhibitor of ER Coregulator PELP1 Targets ER+ Breast Cancer.Cancer research · 2022Article
- SETDB1 interactions with PELP1 contributes to breast cancer endocrine therapy resistance.Breast cancer research : BCR · 2022Article
- Epigenetic Factors as Etiological Agents, Diagnostic Markers, and Therapeutic Targets for Luminal Breast Cancer.Biomedicines · 2022Review
- The ERRα-VDR axis promotes calcitriol degradation and estrogen signaling in breast cancer cells, while VDR-CYP24A1-ERRα overexpression correlates with poor prognosis in patients with basal-like breast cancer.Molecular oncology · 2022Article
- A state-of-the-art review on LSD1 and its inhibitors in breast cancer: Molecular mechanisms and therapeutic significance.Frontiers in pharmacology · 2022Review
- Interaction of transcription factor AP-2 gamma with proto-oncogene PELP1 promotes tumorigenesis by enhancing RET signaling.Molecular oncology · 2021Article
- Role of estrogen receptor coregulators in endocrine resistant breast cancer.Exploration of targeted anti-tumor therapy · 2021Article
- A Prognostic Autophagy-Related Gene Pair Signature and Small-Molecule Drugs for Hepatocellular Carcinoma.Frontiers in genetics · 2021Article
- Tamoxifen induces stem-like phenotypes and multidrug resistance by altering epigenetic regulators in ERα+ breast cancer cells.Stem cell investigation · 2020Article
- Estrogen receptor coregulator binding modulator (ERX-11) enhances the activity of CDK4/6 inhibitors against estrogen receptor-positive breast cancers.Breast cancer research : BCR · 2019Article
- PELP1 Suppression Inhibits Gastric Cancer Through Downregulation of c-Src-PI3K-ERK Pathway.Frontiers in oncology · 2019Article
Corrections and comments
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- Erratum issued
Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
introductionThe estrogen receptor (ER) co-regulator proline glutamic acid and leucine-rich protein 1 (PELP1) is a proto-oncogene that modulates epigenetic changes on ER target gene promoters via interactions with lysine-specific histone demethylase 1 (KDM1). In this study, we assessed the therapeutic potential of targeting the PELP1-KDM1 axis in vivo using liposomal (1,2-dioleoyl-sn-glycero-3-phosphatidylcholine; DOPC) siRNA to downregulate PELP1 expression and KDM1 inhibitors, pargyline and N-((1S)-3-(3-(trans-2-aminocyclopropyl)phenoxy)-1-(benzylcarbamoyl)propyl)benzamide using preclinical models.
methodsPreclinical xenograft models were used to test the efficacy of drugs in vivo. Ki-67 and terminal deoxynucleotidyl transferase dUTP nick end-labeling immunohistochemical analysis of epigenetic markers was performed on tumor tissues. The in vitro effect of PELP1-KDM axis blockers was tested using proliferation, reporter gene, chromatin immunoprecipitation and real-time RT-PCR assays. The efficacy of the KDM1 targeting drugs alone or in combination with letrozole and tamoxifen was tested using therapy-resistant model cells.
resultsTreatment of ER-positive xenograft-based breast tumors with PELP1-siRNA-DOPC or pargyline reduced tumor volume by 58.6% and 62%, respectively. In a postmenopausal model, in which tumor growth is stimulated solely by local estrogen synthesis, daily pargyline treatment reduced tumor volume by 78%. Immunohistochemical analysis of excised tumors revealed a combined decrease in cellular proliferation, induction of apoptosis and upregulation of inhibitory epigenetic modifications. Pharmacological inhibition of KDM1 in vitro increased inhibitory histone mark dimethylation of histone H3 at lysine 9 (H3K9me2) and decreased histone activation mark acetylation of H3K9 (H3K9Ac) on ER target gene promoters. Combining KDM1 targeting drugs with current endocrine therapies substantially impeded growth and restored sensitivity of therapy-resistant breast cancer cells to treatment.
conclusionOur results suggest inhibition of PELP1-KDM1-mediated histone modifications as a potential therapeutic strategy for blocking breast cancer progression and therapy resistance.
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