Lysophosphatidic acid induces prostate cancer PC3 cell migration via activation of LPA(1), p42 and p38alpha.
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.
Hao
Feng
F
Department of Pathobiology, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN 37996, USA.
Tan
Mingqi
M
Xu
Xuemin
X
Han
Jiahuai
J
Miller
Duane D
DD
Tigyi
Gabor
G
Cui
Mei-Zhen
MZ
D002465:Cell Movement / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008246:Lysophospholipids / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048308:Mitogen-Activated Protein Kinase 14 / Q000378:metabolism*; D037342:Pertussis Toxin / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D034741:RNA, Small Interfering / Q000378:metabolism; D049368:Receptors, Lysophosphatidic Acid / Q000235:genetics / Q000378:metabolism*
D008246:Lysophospholipids; D034741:RNA, Small Interfering; D049368:Receptors, Lysophosphatidic Acid; D037342:Pertussis Toxin; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048308:Mitogen-Activated Protein Kinase 14; D019204:GTP-Binding Proteins; C032881:lysophosphatidic acid