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

作者: Yasuhiro Kishi , Shinichi Okudaira , Masayuki Tanaka , Kotaro Hama , Dai Shida

DOI: 10.1074/JBC.M601803200

关键词: CellBiologyTransfectionCancer cellCell migrationBiochemistryAutotaxinLysophosphatidic acidCancer researchGliomaAutocrine signalling

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

参考文章(50)
Yoh Takuwa, Dai Shida, Nelson Hirokazu Tsuno, Hironori Yamaguchi, Toshiaki Watanabe, Yurai Okaji, Joji Kitayama, Hirokazu Nagawa, Lysophosphatidic acid (LPA) enhances the metastatic potential of human colon carcinoma DLD1 cells through LPA1 Cancer Research. ,vol. 63, pp. 1706- 1711 ,(2003)
M L Stracke, H C Krutzsch, E J Unsworth, A Arestad, V Cioce, E Schiffmann, L A Liotta, Identification, Purification, and Partial Sequence Analysis of Autotaxin, a Novel Motility-stimulating Protein* Journal of Biological Chemistry. ,vol. 267, pp. 2524- 2529 ,(1992) , 10.1016/S0021-9258(18)45911-X
So Young Yang, Jangsoon Lee, Chang Gyo Park, Seonghwan Kim, Sungyoul Hong, Hyun Cheol Chung, Seong Ki Min, Jeung Whan Han, Hyang Woo Lee, Hoi Young Lee, Expression of autotaxin (NPP-2) is closely linked to invasiveness of breast cancer cells. Clinical & Experimental Metastasis. ,vol. 19, pp. 603- 608 ,(2002) , 10.1023/A:1020950420196
Lance A. Liotta, Andrew McMarlin, Mary L. Stracke, Suk Woo Nam, Young Sik Kim, Elliott Schiffmann, Timothy Clair, Autotaxin (NPP-2), a metastasis-enhancing motogen, is an angiogenic factor Cancer Research. ,vol. 61, pp. 6938- 6944 ,(2001)
Jukka Westermarck, Veli‐Matti Kähäri, Regulation of matrix metalloproteinase expression in tumor invasion The FASEB Journal. ,vol. 13, pp. 781- 792 ,(1999) , 10.1096/FASEBJ.13.8.781
Alf Giese, Michael E. Berens, Melinda A. Loo, Monique D. Rief, Determinants of Human Astrocytoma Migration Cancer Research. ,vol. 54, pp. 3897- 3904 ,(1994)
Takamitsu Fujimaki, Masao Matsutani, Osamu Nakamura, Akio Asai, Nobuaki Funada, Morio Koike, Hiromu Segawa, Kouichi Aritake, Takanori Fukushima, Shuntaro Houjo, Akira Tamura, Keiji Sano, Correlation between bromodeoxyuridine-labeling indices and patient prognosis in cerebral astrocytic tumors of adults Cancer. ,vol. 67, pp. 1629- 1634 ,(1991) , 10.1002/1097-0142(19910315)67:6<1629::AID-CNCR2820670626>3.0.CO;2-E
James W Goding, Robert Terkeltaub, Michele Maurice, Philippe Deterre, Adnan Sali, Sabina I. Belli, Ecto-phosphodiesterase/pyrophosphatase of lymphocytes and non-lymphoid cells: structure and function of the PC-1 family. Immunological Reviews. ,vol. 161, pp. 11- 26 ,(1998) , 10.1111/J.1600-065X.1998.TB01568.X
Songzhu An, Thieu Bleu, Olivia G. Hallmark, Edward J. Goetzl, Characterization of a Novel Subtype of Human G Protein-coupled Receptor for Lysophosphatidic Acid Journal of Biological Chemistry. ,vol. 273, pp. 7906- 7910 ,(1998) , 10.1074/JBC.273.14.7906
C. Mulder, L.-O. Wahlund, T. Teerlink, M. Blomberg, R. Veerhuis, G. J. van Kamp, P. Scheltens, P. G. Scheffer, Decreased lysophosphatidylcholine/phosphatidylcholine ratio in cerebrospinal fluid in Alzheimer's disease. Journal of Neural Transmission. ,vol. 110, pp. 949- 955 ,(2003) , 10.1007/S00702-003-0007-9