Format

Send to

Choose Destination
Biochim Biophys Acta. 2007 Jul;1771(7):883-92. Epub 2007 Apr 24.

Lysophosphatidic acid induces prostate cancer PC3 cell migration via activation of LPA(1), p42 and p38alpha.

Author information

1
Department of Pathobiology, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN 37996, USA.

Abstract

Prostate cancer cell migration is an essential event both in the progression of prostate cancer and in the steps leading to metastasis. We report here that lysophosphatidic acid (LPA), a potent bioactive phospholipid, induces prostate cancer PC3 cell migration via the activation of the LPA(1) receptor, which is linked to a PTX-sensitive activation mechanism of the mitogen-activated protein kinases (MAPK). Our results demonstrate that parallel activation of ERK1/2 and p38, but not JNK, is responsible for LPA-stimulated PC3 cell migration. Furthermore, using small interfering RNA (siRNA) technology, and overexpressing dominant-negative mutants of p38 MAPK isotypes of alpha, beta, gamma and delta, we have identified that the activation of ERK2 (p42) and p38alpha, but not of ERK1 and the other isoforms of p38 MAPK, is required for LPA-induced migration. Our study provides the first evidence for a functional role of p42 and p38alpha in LPA-induced mammalian cell migration, and also demonstrates, for the first time, that the receptor LPA(1) mediates prostate cancer cell migration. The results of the present study suggest that LPA, the receptor LPA(1), ERK2 and p38alpha are important regulators for prostate cancer cell invasion and thus could play a significant role in the development of metastasis.

PMID:
17531530
PMCID:
PMC3446792
DOI:
10.1016/j.bbalip.2007.04.010
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center