Synergistic induction of cancer cell migration regulated by Gbetagamma and phosphatidylinositol 3-kinase
Experimental & Molecular Medicine
;
: 483-491, 2012.
Artigo
em Inglês
| WPRIM
| ID: wpr-192554
ABSTRACT
Phosphatidylinositol 3-kinase (PI3K) is essential for both G protein-coupled receptor (GPCR)- and receptor tyrosine kinase (RTK)-mediated cancer cell migration. Here, we have shown that maximum migration is achieved by full activation of phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 1 (P-Rex1) in the presence of Gbetagamma and PI3K signaling pathways. Lysophosphatidic acid (LPA)-induced migration was higher than that of epidermal growth factor (EGF)-induced migration; however, LPA-induced activation of Akt was lower than that stimulated by EGF. LPA-induced migration was partially blocked by either Gbetagamma or RTK inhibitor and completely blocked by both inhibitors. LPA-induced migration was synergistically increased in the presence of EGF and vice versa. In correlation with these results, sphingosine-1-phosphate (S1P)-induced migration was also synergistically induced in the presence of insulin-like growth factor-1 (IGF-1). Finally, silencing of P-Rex1 abolished the synergism in migration as well as in Rac activation. Moreover, synergistic activation of MMP-2 and cancer cell invasion was attenuated by silencing of P-Rex1. Given these results, we suggest that P-Rex1 requires both Gbetagamma and PI3K signaling pathways for synergistic activation of Rac, thereby inducing maximum cancer cell migration and invasion.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Lisofosfolipídeos
/
Transdução de Sinais
/
Movimento Celular
/
Fosfatidilinositol 3-Quinases
/
Fatores de Troca do Nucleotídeo Guanina
/
Linhagem Celular Tumoral
/
Subunidades beta da Proteína de Ligação ao GTP
/
Subunidades gama da Proteína de Ligação ao GTP
/
Receptores Acoplados a Proteínas G
/
Ativação Enzimática
Limite:
Humanos
Idioma:
Inglês
Revista:
Experimental & Molecular Medicine
Ano de publicação:
2012
Tipo de documento:
Artigo
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