ArticleJournal of experimental & clinical cancer research : CR2022
The PRMT5-LSD1 axis confers Slug dual transcriptional activities and promotes breast cancer progression.
Article in Journal of experimental & clinical cancer research : CR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 48 citations in OpenAlex.
- Fast-Food Component-Induced Epigenetic Modifications Modulate Immunotherapy in Metastatic Breast Cancer.ACS omega · 2026Article
- Epigenetic remodeling during UV exposure: high resolution analysis of histone post-translational modifications in a DNA binding protein 2 mutant model.Histochemistry and cell biology · 2026Article
- PRMT5 as a Key Driver of Stemness and Metastatic Potential in Triple-Negative Breast Cancer.Biomolecules · 2026Review
- CIITA/PRMT5 promote CD4BMC medicine · 2026Article
- HBx-mediated GPT2 suppression promotes liver cancer development by downregulating ADH1A.Cancer biology & medicine · 2026Article
- LSD1-ESM1 regulates extravillous trophoblast function through metabolic reprogramming in recurrent spontaneous abortion.Journal of assisted reproduction and genetics · 2026Article
- Protein arginine methyltransferases in cancer: mechanisms, functions, and therapeutic opportunities.Journal of biomedical science · 2026Review
- DDX10 RNA Helicase: Structure, Function, and Oncogenic Roles Across Solid and Hematologic Tumors.Genes · 2026Review
- PCK2-Mediated PQBP1 Lactylation Promotes Asthmatic Inflammation through PRMT5 Inhibition.Research (Washington, D.C.) · 2026Article
- Protein arginine methyltransferase 5 as a novel therapeutic target in solid tumors.Genes & diseases · 2026Review
- Review
- Arginine methylation in cancer: mechanisms and therapeutic implications.Biomarker research · 2025Review
- [Inhibition of BRD4 promotes migration of esophageal squamous cell carcinoma cells with low ACC1 expression].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- Review
- PRMT5 Promotes Pancreatic Cancer Tumorigenesis via Positive PRMT5/C-Myc Feedback Loop.MedComm · 2025Article
- PRMT5-regulated splicing of DNA repair genes drives chemoresistance in breast cancer stem cells.Oncogene · 2025Article
- Copy number amplification of FLAD1 promotes the progression of triple-negative breast cancer through lipid metabolism.Nature communications · 2025Article
- Targeting PRMT5 through PROTAC for the treatment of triple-negative breast cancer.Journal of experimental & clinical cancer research : CR · 2024Article
- Role of PRMT1 and PRMT5 in Breast Cancer.International journal of molecular sciences · 2024Review
- The ubiquitin ligase UBR4 and the deubiquitylase USP5 modulate the stability of DNA mismatch repair protein MLH1.The Journal of biological chemistry · 2024Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundDownregulation of epithelial markers and upregulation of mesenchymal markers are the characteristics of the epithelial to mesenchymal transition (EMT) program, which provides the metastatic advantage of breast cancer. However, the mechanism underlying the switch of EMT markers remains poorly understood.
methodsIn this study, we used the affinity purification and mass spectrometry coupled approach to identify the interactome of Slug. CoIP, GST-pulldown, ChIP, Re-ChIP, qPCR and Immunoblot were used to investigate the underlying mechanism of Slug-PRMT5-LSD1 complex. The role of PRMT5 and LSD1 in breast cancer progression was evaluated both in vivo and in vitro.
resultsHere we found that the transcription factor Slug associates with PRMT5 and LSD1 in a complex and facilitates the breast cancer invasion in vitro. Mechanistically, PRMT5 and LSD1 work with Slug to exert dual transcriptional activities to inhibit E-cadherin expression by PRMT5-catalyzed H4R3me2s and LSD1-mediated demethylation of H3K4me2 on the E-cadherin (CDH1) promoter, and activate vimentin (VIM) expression via PRMT5-driven H3R2me2s and LSD1-mediated removal of H3K9me2. Importantly, PRMT5 and LSD1 are coordinately expressed in breast cancer patients and pharmacologic perturbation of both PRMT5 and LSD1 shows a synergetic effect on the inhibition of breast tumor growth and metastasis in vivo.
conclusionsOur study suggests that PRMT5 and LSD1 function as a dual epigenetic modifier to promote Slug induced EMT program, suggesting that the inhibition of PRMT5 and LSD1 presents a potential therapeutic strategy against cancer metastasis.
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