Molecular tools that block maturation of the nuclear lamin A and decelerate cancer cell migration |
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Authors: | Alexios N Matralis Dimitrios Xanthopoulos Geneviève Huot Stéphane Lopes-Paciencia Charles Cole Hugo de Vries Gerardo Ferbeyre Youla S Tsantrizos |
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Institution: | 1. Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montreal, QC H3A 0B8, Canada;2. Département de Biochimie et medicine moléculaire, CRCHUM, Université de Montréal, C.P. 6128, Succ. Centre-Ville, Montréal, Québec H3C 3J7, Canada;3. Department of Biochemistry, McGill University, 3649 Promenade Sir William Osler, Montreal, QC H3G 0B1, Canada |
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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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Keywords: | Prelamin A Zinc metalloprotease STE24 ZPMSTE24 Lamin A |
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