Autotaxin is overexpressed in glioblastoma multiforme and contributes to cell motility of glioblastoma by converting lysophosphatidylcholine TO lysophosphatidic acid

Yasuhiro Kishi, Shinichi Okudaira, Masayuki Tanaka, Kotaro Hama, Dai Shida, Joji Kitayama, Takao Yamori, Junken Aoki, Takamitsu Fujimaki, Hiroyuki Arai

Research output: Contribution to journalArticlepeer-review

191 Citations (Scopus)

Abstract

Autotaxin (ATX) is a multifunctional phosphodiesterase originally isolated from melanoma cells as a potent cell motility-stimulating factor. ATX is identical to lysophospholipase D, which produces a bioactive phospholipid, lysophosphatidic acid (LPA), from lysophosphatidylcholine (LPC). Although enhanced expression of ATX in various tumor tissues has been repeatedly demonstrated, and thus, ATX is implicated in progression of tumor, the precise role of ATX expressed by tumor cells was unclear. In this study, we found that ATX is highly expressed in glioblastoma multiforme (GBM), the most malignant glioma due to its high infiltration into the normal brain parenchyma, but not in tissues from other brain tumors. In addition, LPA1, an LPA receptor responsible for LPA-driven cell motility, is predominantly expressed in GBM. One of the glioblastomas that showed the highest ATX expression (SNB-78), as well as ATX-stable transfectants, showed LPA1-dependent cell migration in response to LPA in both Boyden chamber and wound healing assays. Interestingly these ATX-expressing cells also showed chemotactic response to LPC. In addition, knockdown of the ATX level using small interfering RNA technique in SNB-78 cells suppressed their migratory response to LPC. These results suggest that the autocrine production of LPA by cancer cell-derived ATX and exogenously supplied LPC contribute to the invasiveness of cancer cells and that LPA1, ATX, and LPC-producing enzymes are potential targets for cancer therapy, including GBM.

Original languageEnglish
Pages (from-to)17492-17500
Number of pages9
JournalJournal of Biological Chemistry
Volume281
Issue number25
DOIs
Publication statusPublished - 2006 Jun 23

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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