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Molecular tools that block maturation of the nuclear lamin A and decelerate cancer cell migration.
Matralis, Alexios N; Xanthopoulos, Dimitrios; Huot, Geneviève; Lopes-Paciencia, Stéphane; Cole, Charles; de Vries, Hugo; Ferbeyre, Gerardo; Tsantrizos, Youla S.
Afiliação
  • Matralis AN; Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montreal, QC H3A 0B8, Canada.
  • Xanthopoulos D; Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montreal, QC H3A 0B8, Canada.
  • Huot G; Département de Biochimie et medicine moléculaire, CRCHUM, Université de Montréal, C.P. 6128, Succ. Centre-Ville, Montréal, Québec H3C 3J7, Canada.
  • Lopes-Paciencia S; Département de Biochimie et medicine moléculaire, CRCHUM, Université de Montréal, C.P. 6128, Succ. Centre-Ville, Montréal, Québec H3C 3J7, Canada.
  • Cole C; Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montreal, QC H3A 0B8, Canada.
  • de Vries H; Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montreal, QC H3A 0B8, Canada.
  • Ferbeyre G; Département de Biochimie et medicine moléculaire, CRCHUM, Université de Montréal, C.P. 6128, Succ. Centre-Ville, Montréal, Québec H3C 3J7, Canada.
  • Tsantrizos YS; Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montreal, QC H3A 0B8, Canada; Department of Biochemistry, McGill University, 3649 Promenade Sir William Osler, Montreal, QC H3G 0B1, Canada. Electronic address: Youla.tsantrizos@mcgill.ca.
Bioorg Med Chem ; 26(20): 5547-5554, 2018 11 01.
Article em En | MEDLINE | ID: mdl-30309670
ABSTRACT
Lamin A contributes to the structure of nuclei in all mammalian cells and plays an important role in cell division and migration. Mature lamin A is derived from a farnesylated precursor protein, known as prelamin A, which undergoes post-translational cleavage catalyzed by the zinc metalloprotease STE24 (ZPMSTE24). Accumulation of farnesylated prelamin A in the nuclear envelope compromises cell division, impairs mitosis and induces an increased expression of inflammatory gene products. ZMPSTE24 has been proposed as a potential therapeutic target in oncology. A library of peptidomimetic compounds were synthesized and screened for their ability to induce accumulation of prelamin A in cancer cells and block cell migration in pancreatic ductal adenocarcinoma cells. The results of this study suggest that inhibitors of lamin A maturation may interfere with cell migration, the biological process required for cancer metastasis.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Movimento Celular / Lamina Tipo A / Peptidomiméticos / Antineoplásicos Limite: Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Movimento Celular / Lamina Tipo A / Peptidomiméticos / Antineoplásicos Limite: Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article