Synthetic triterpenoids inhibit GSK3ß activity and localization and affect focal adhesions and cell migration.
Biochim Biophys Acta Mol Cell Res
; 1864(7): 1274-1284, 2017 Jul.
Article
em En
| MEDLINE
| ID: mdl-28366661
ABSTRACT
Synthetic triterpenoids are a class of anti-cancer compounds that target many cellular functions, including apoptosis and cell growth in both cell culture and animal models. We have shown that triterpenoids inhibit cell migration in part by interfering with Arp2/3-dependent branched actin polymerization in lamellipodia (To et al., 2010). Our current studies reveal that Glycogen Synthase Kinase 3 beta (GSK3ß), a kinase that regulates many cellular processes, including cell adhesion dynamics, is a triterpenoid-binding protein. Furthermore, triterpenoids were observed to inhibit GSK3ß activity and increase cellular focal adhesion size. To further examine whether these effects on focal adhesions in triterpenoid-treated cells were GSK3ß-dependent, GSK3ß inhibitors (lithium chloride and SB216763) were used to examine cell adhesion and morphology as well as cell migration. Our results showed that GSK3ß inhibitors also altered cell adhesion sizes. Moreover, these inhibitors blocked cell migration and displaced proteins at the leading edge of migrating cells, consistent with what was observed in triterpenoid-treated cells. Therefore, the triterpenoids may affect cell migration via a mechanism that targets and alters the activity and localization of GSK3ß.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ácido Oleanólico
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Movimento Celular
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Adesões Focais
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Glicogênio Sintase Quinase 3 beta
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Imidazóis
Limite:
Animals
Idioma:
En
Revista:
Biochim Biophys Acta Mol Cell Res
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Canadá