Autotaxin Plays a Protective Role in Cancer Cells Treated with Taxol

Researchers in Edmonton, Canada have discovered that autotaxin (ATX) can protect cancer cells from the apoptotic effects of Taxol, a commonly used chemotherapeutic agent in breast cancer treatment. The study, published in Oncogene, found that ATX converts extracellular lysophosphatidylcholine (LPC) into lysophosphatidate (LPA), which has been reported to affect cell signaling through its own G-protein-coupled receptors. The team, led by N. Samadi from the University of Alberta, investigated the interactions of ATX, LPC, and LPA on Taxol-induced apoptosis in MCF-7 breast cancer cells and MDA-MB-435 melanoma cells.

Key Takeaways:

• Autotaxin (ATX) protects cancer cells from Taxol-induced apoptosis by converting LPC into LPA.
• LPA strongly antagonizes Taxol-induced apoptosis through stimulating phosphatidylinositol 3-kinase and inhibiting ceramide formation.
• Inhibiting ATX activity blocked the protection against apoptosis, suggesting that therapeutic inhibition of ATX could improve the efficacy of Taxol.
• MCF-7 breast cancer cells do not secrete significant ATX, but addition of incubation medium from MDA-MB-435 melanoma cells or recombinant ATX enabled LPC to inhibit Taxol-induced apoptosis.
• The study supports the hypothesis that therapeutic inhibition of ATX activity could improve the efficacy of Taxol as a chemotherapeutic agent for cancer treatment.
• The researchers found that LPA partially reversed the Taxol-induced arrest in the G2/M phase of the cell cycle.

Statistics:

• 1028-39: the page numbers of the study in Oncogene (2009).
• 7: the issue number in which the study was published in Oncogene.
• 345 Park Avenue South, New York, NY 10010-1707, USA: the publisher contact information for Oncogene.
• 2009: the year the study was published.

Sources:

• "Autotaxin protects MCF-7 breast cancer and MDA-MB-435 melanoma cells against Taxol-induced apoptosis." Oncogene (2009);28(7):1028-39.
• N. Samadi, University of Alberta, Dept. of Laboratory Medicine and Pathology, Edmonton, Alberta, Canada.
• Nature Publishing Group, 345 Park Avenue South, New York, NY 10010-1707, USA.