Lysophosphatidic acid induces prostate cancer PC3 cell migration via activation of LPA1, p42 and p38α

Feng Hao, Mingqi Tan, Xuemin Xu, Jiahuai Han, Duane Miller, Gabor Tigyi, Mei Zhen Cui

Research output: Contribution to journalArticle

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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 LPA1 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 α, β, γ and δ, we have identified that the activation of ERK2 (p42) and p38α, 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 p38α in LPA-induced mammalian cell migration, and also demonstrates, for the first time, that the receptor LPA1 mediates prostate cancer cell migration. The results of the present study suggest that LPA, the receptor LPA1, ERK2 and p38α are important regulators for prostate cancer cell invasion and thus could play a significant role in the development of metastasis.

Original languageEnglish (US)
Pages (from-to)883-892
Number of pages10
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1771
Issue number7
DOIs
StatePublished - Jul 1 2007

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Cell Movement
Lysophosphatidic Acid Receptors
Prostatic Neoplasms
p38 Mitogen-Activated Protein Kinases
Neoplasm Metastasis
Mitogen-Activated Protein Kinases
Small Interfering RNA
Phospholipids
Protein Isoforms
lysophosphatidic acid
Technology

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Lysophosphatidic acid induces prostate cancer PC3 cell migration via activation of LPA1, p42 and p38α. / Hao, Feng; Tan, Mingqi; Xu, Xuemin; Han, Jiahuai; Miller, Duane; Tigyi, Gabor; Cui, Mei Zhen.

In: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, Vol. 1771, No. 7, 01.07.2007, p. 883-892.

Research output: Contribution to journalArticle

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AU - Cui, Mei Zhen

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