Therapeutic targeting of protein arginine methyltransferases reduces breast cancer progression by disrupting angiogenic pathways

dc.contributor.authorMaphalala, Kamohelo
dc.contributor.authorRamali, Dakalo Portia
dc.contributor.authorMaebele, Lorraine Tshegofatso
dc.contributor.authorMulaudzi, Thanyani Victor
dc.contributor.authorMabeta, Peaceful Lucy
dc.contributor.authorDlamini, Zodwa
dc.contributor.authorDamane, Botle Precious
dc.contributor.emailbotle.damane@up.ac.za
dc.date.accessioned2025-08-27T06:14:00Z
dc.date.available2025-08-27T06:14:00Z
dc.date.issued2025-09
dc.descriptionDATA AVAILABILITY : No data was used for the research described in the article.
dc.description.abstractProtein arginine methylation is an epigenetic modification involved in transcription, splicing and signal transduction and is mediated by protein arginine methyltransferases (PRMTs). PRMTs regulate various tumor angiogenesis pathways, including vascular endothelial growth factor receptor-2 (VEGFR-2) signaling. PRMT1, PRMT4, and PRMT5 activate distinct stages of angiogenesis. For example, inhibiting PRMT5 suppresses VEGF-induced vessel sprouting in experimental models while impairing hypoxia-inducible factor 1-alpha (HIF-1α) stability and VEGFR-2 phosphorylation. PRMT1 and PRMT4 similarly influence VEGF isoform expression, leading to increased angiogenesis. Targeting PRMTs in experimental models results in suppressed angiogenesis and reduced cancer progression. Several small-molecule PRMT inhibitors, including GSK3326595 and EPZ015666, have entered early-phase clinical trials for solid tumors. These agents show promise in inhibiting tumor angiogenesis, although there are toxicity concerns. This review examines the mechanistic basis and therapeutic rationale for targeting PRMTs in breast cancer and discusses combination approaches to overcome resistance. We integrate preclinical and emerging clinical data to highlight the potential antiangiogenic and tumor-suppressive effects of PRMT inhibitors, providing insights for future therapeutic strategies for breast cancer. HIGHLIGHTS • Dysregulated arginine methylation may drive aberrant angiogenic signaling pathways in breast cancer. • Arginine methylation controls endothelial cell functions via cytokines, growth factors, and related mediators. • Inhibiting arginine methylation may help counteract dysregulated angiogenic signaling in breast cancer.
dc.description.departmentSurgery
dc.description.departmentPhysiology
dc.description.departmentMedical Oncology
dc.description.librarianhj2025
dc.description.sdgSDG-03: Good health and well-being
dc.description.sponsorshipThe National Research Foundation, South African Medical Research Council (SAMRC) Researcher Development Award and the University of Pretoria Capacity Development Program.
dc.description.urihttps://www.elsevier.com/locate/bbrep
dc.identifier.citationMaphalala, K., Ramali, D.P., Maebele, L.T. et al. 2025, 'Therapeutic targeting of protein arginine methyltransferases reduces breast cancer progression by disrupting angiogenic pathways', Biochemistry and Biophysics Reports, vol. 43, art. 102172, pp. 1-13, doi : 10.1016/j.bbrep.2025.102172.
dc.identifier.issn2405-5808 (online)
dc.identifier.other10.1016/j.bbrep.2025.102172
dc.identifier.urihttp://hdl.handle.net/2263/104011
dc.language.isoen
dc.publisherElsevier
dc.rights© 2025 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
dc.subjectProtein arginine methylation
dc.subjectProtein arginine methyltransferases (PRMTs)
dc.subjectBreast cancer
dc.subjectAngiogenesis
dc.subjectAngiogenic signaling pathways
dc.subjectHypoxia
dc.subjectVascularization
dc.subjectProtein arginine methyltransferase inhibitors
dc.titleTherapeutic targeting of protein arginine methyltransferases reduces breast cancer progression by disrupting angiogenic pathways
dc.typeArticle

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