Molecular tools that block maturation of the nuclear lamin A and decelerate cancer cell migration.
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
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Lamina Tipo A
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Peptidomiméticos
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Antineoplásicos
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article