Lysophosphatidic Acid and Autotaxin Stimulate Cell Motility of Neoplastic and Non-neoplastic Cells through LPA

Kotaro Hama, Junken Aoki, Masahiro Fukaya, Yasuhiro Kishi, Teruyuki Sakai, Rika Suzuki, Hideo Ohta, Takao Yamori, Masahiko Watanabe, Jerold Chun, Hiroyuki Arai

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222 Citations (Scopus)

Abstract

Autotaxin (ATX) is a tumor cell motility-stimulating factor originally isolated from melanoma cell supernatant that has been implicated in regulation of invasive and metastatic properties of cancer cells. Recently, we showed that ATX is identical to lysophospholipase D, which converts lysophosphatidylcholine to a potent bioactive phospholipid mediator, lysophosphatidic acid (LPA), raising the possibility that autocrine or paracrine production of LPA by ATX contributes to tumor cell motility. Here we demonstrate that LPA and ATX mediate cell motility-stimulating activity through the LPA receptor, LPA 1. In fibroblasts isolated from lpa1-/- mice, but not from wild-type of lpa2-/-, cell motility stimulated with LPA and ATX was completely absent. In the lpa1 -/- cells, LPA-stimulated lamellipodia formation was markedly diminished with a concomitant decrease in Rac1 activation. LPA stimulated the motility of multiple human cancer cell lines expressing LPA1, and the motility was attenuated by an LPA1-selective antagonist, Ki16425. The present study suggests that ATX and LPA1 represent potential targets for cancer therapy.

Original languageEnglish
Pages (from-to)17634-17639
Number of pages6
JournalJournal of Biological Chemistry
Volume279
Issue number17
DOIs
Publication statusPublished - 2004 Apr 23

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Hama, K., Aoki, J., Fukaya, M., Kishi, Y., Sakai, T., Suzuki, R., Ohta, H., Yamori, T., Watanabe, M., Chun, J., & Arai, H. (2004). Lysophosphatidic Acid and Autotaxin Stimulate Cell Motility of Neoplastic and Non-neoplastic Cells through LPA. Journal of Biological Chemistry, 279(17), 17634-17639. https://doi.org/10.1074/jbc.M313927200