Synergistic induction of cancer cell migration regulated by Gbetagamma and phosphatidylinositol 3-kinase
Experimental & Molecular Medicine
;
: 483-491, 2012.
Article
in English
| 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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Lysophospholipids
/
Signal Transduction
/
Cell Movement
/
Phosphatidylinositol 3-Kinases
/
Guanine Nucleotide Exchange Factors
/
Cell Line, Tumor
/
GTP-Binding Protein beta Subunits
/
GTP-Binding Protein gamma Subunits
/
Receptors, G-Protein-Coupled
/
Enzyme Activation
Limits:
Humans
Language:
English
Journal:
Experimental & Molecular Medicine
Year:
2012
Type:
Article
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