Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
Volume 1771, Issue 7, Pages 883-892Publisher
ELSEVIER
DOI: 10.1016/j.bbalip.2007.04.010
Keywords
lysophosphatidic acid; receptors; cell migration; protein kinases and prostate cancer cells
Funding
- NCI NIH HHS [R01 CA092160-08, CA92160, R01 CA092160] Funding Source: Medline
- NHLBI NIH HHS [R01 HL074341-03, R01 HL074341, HL074341] Funding Source: Medline
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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 activati on of the LPA, receptor, which is linked to a PTX-seiisitive 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-stiniulated 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 p38 alpha, 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 p38 alpha 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 p38 alpha are important regulators for prostate cancer cell invasion and thus could play a significant role in the development of metastasis.(c) 2007 Elsevier B.V. All rights reserved.
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