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Epigenetic arginine methylation in breast cancer: emerging therapeutic strategies.
Wang, Shu-Ching M; Dowhan, Dennis H; Muscat, George E O.
Afiliación
  • Wang SM; Cell Biology and Molecular Medicine Division, The University of Queensland, Institute for Molecular Bioscience, St Lucia, Australia.
  • Dowhan DH; Cell Biology and Molecular Medicine Division, The University of Queensland, Institute for Molecular Bioscience, St Lucia, Australia.
  • Muscat GEO; Cell Biology and Molecular Medicine Division, The University of Queensland, Institute for Molecular Bioscience, St Lucia, Australia.
J Mol Endocrinol ; 62(3): R223-R237, 2019 04 01.
Article en En | MEDLINE | ID: mdl-30620710
Breast cancer is a heterogeneous disease, and the complexity of breast carcinogenesis is associated with epigenetic modification. There are several major classes of epigenetic enzymes that regulate chromatin activity. This review will focus on the nine mammalian protein arginine methyltransferases (PRMTs) and the dysregulation of PRMT expression and function in breast cancer. This class of enzymes catalyse the mono- and (symmetric and asymmetric) di-methylation of arginine residues on histone and non-histone target proteins. PRMT signalling (and R methylation) drives cellular proliferation, cell invasion and metastasis, targeting (i) nuclear hormone receptor signalling, (ii) tumour suppressors, (iii) TGF-ß and EMT signalling and (iv) alternative splicing and DNA/chromatin stability, influencing the clinical and survival outcomes in breast cancer. Emerging reports suggest that PRMTs are also implicated in the development of drug/endocrine resistance providing another prospective avenue for the treatment of hormone resistance and associated metastasis. The complexity of PRMT signalling is further underscored by the degree of alternative splicing and the scope of variant isoforms (with distinct properties) within each PRMT family member. The evolution of PRMT inhibitors, and the ongoing clinical trials of PRMT inhibitors against a subgroup of solid cancers, coupled to the track record of lysine methyltransferases inhibitors in phase I/II clinical trials against cancer underscores the potential therapeutic utility of targeting PRMT epigenetic enzymes to improve survival outcomes in aggressive and metastatic breast cancer.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Arginina / Neoplasias de la Mama / Epigénesis Genética Límite: Animals / Female / Humans Idioma: En Revista: J Mol Endocrinol Asunto de la revista: BIOLOGIA MOLECULAR / ENDOCRINOLOGIA Año: 2019 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Arginina / Neoplasias de la Mama / Epigénesis Genética Límite: Animals / Female / Humans Idioma: En Revista: J Mol Endocrinol Asunto de la revista: BIOLOGIA MOLECULAR / ENDOCRINOLOGIA Año: 2019 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Reino Unido