A PAK4-LIMK1 pathway drives prostate cancer cell migration downstream of HGF.
Cell Signal
; 20(7): 1320-8, 2008 Jul.
Article
en En
| MEDLINE
| ID: mdl-18424072
ABSTRACT
Hepatocyte growth factor (HGF) is associated with tumour progression and increases the invasiveness of prostate carcinoma cells. Cell migration and invasion requires reorganisation of the actin cytoskeleton; processes mediated by the Rho family GTPases. p21 activated kinase 4 (PAK4), an effector of the Rho family protein Cdc42, is activated downstream of HGF. We report here the novel finding that in prostate cancer cells PAK4 binds to and phosphorylates LIM kinase 1 (LIMK1) in an HGF-dependent manner. We show for the first time that variations in the level of PAK4 expression change the level of cofilin phosphorylation in cells, a change we correlate with LIMK1 activity, cell morphology and migratory behaviour. We identify for the first time a direct and localised interaction between PAK4 and LIMK1 within cells using FRET FLIM. Moreover we show here that HGF mediates this interaction which is concentrated in small foci at the cell periphery. PAK4 and LIMK1 act synergistically to increase cell migration speed, whilst a reduction in PAK4 expression decreases cell speed. It is well established that unphosphorylated (active) cofilin is a required to drive cell migration. Our results support a model whereby HGF-stimulated cell migration also requires a cofilin phosphorylation step that is mediated by PAK4.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias de la Próstata
/
Movimiento Celular
/
Factor de Crecimiento de Hepatocito
/
Quinasas Lim
/
Quinasas p21 Activadas
Tipo de estudio:
Prognostic_studies
Límite:
Humans
/
Male
Idioma:
En
Revista:
Cell Signal
Año:
2008
Tipo del documento:
Article
País de afiliación:
Reino Unido