First published online July 12, 2005
Journal of Cell Science 118, 1403e (2005)
© The Company of Biologists Limited
Autotaxin's secret life
Autotaxin (NPP2) is a tumour-associated lysophospholipase whose upregulation correlates with invasiveness of cancer cells. It is an attractive target for cancer therapy because it generates extracellular lysophosphatidic acid (LPA), which promotes metastasis at several levels – LPA stimulates cell proliferation, survival, migration and angiogenesis. Autotaxin was thought, like its close relative NPP1, to be a transmembrane protein. Mathieu Bollen and co-workers now show that it is instead secreted, and this has important implications (see p. 3081). The authors observe autotaxin in the Golgi apparatus of HEK293 cells and find that the vast majority ends up in the culture medium. They have used domain swapping and mutagenesis to define the signal peptide that directs it into the secretory pathway. Moreover, they demonstrate that the protein is synthesised as a pre-pro-enzyme, in which the N-terminal signal peptide is followed by an octapeptide that is subsequently cleaved by proprotein convertases such as furin. The processed enzyme is more active than its precursor. Bollen and co-workers therefore suggest that anticancer therapies that target autotaxin could be directed against its synthesis, processing or enzymatic activity.
Related articles in JCS:
- Proteolytic maturation and activation of autotaxin (NPP2), a secreted metastasis-enhancing lysophospholipase D
- Silvia Jansen, Cristiana Stefan, John W. M. Creemers, Etienne Waelkens, Aleyde Van Eynde, Willy Stalmans, and Mathieu Bollen
JCS 2005 118: 3081-3089.
[Abstract]
[Full Text]
