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Permanent link (DOI): https://doi.org/10.7939/R3HT2GR44
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Brain fatty acid-binding protein and ω-3/ω-6 fatty acids: Mechanistic insight into the poor prognosis of malignant glioma cell migration Open Access
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Beaulieu, Michael J.
Field, Catherine J.
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Fatty Acid-Binding Protein
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Malignant gliomas (MG) are highly infiltrative tumors that consistently recur despite aggressive treatment. Brain fatty acid-binding protein (FABP7), which binds docosahexaenoic acid (DHA) and arachidonic acid (AA), localizes to sites of tumor infiltration and is associated with a poor prognosis in MG. Manipulation of FABP7 expression in MG cell lines affects cell migration, suggesting a role for FABP7 in tumor infiltration and recurrence. Here, we show that DHA inhibits and AA stimulates migration in an FABP7-dependent manner in U87 MG cells. We demonstrate that DHA binds to and sequesters FABP7 to the nucleus, resulting in decreased cell migration. This anti-migratory effect is partially dependent on peroxisome proliferator-activated receptor γ, a DHA-activated transcription factor. Conversely, AA-bound FABP7 stimulates cell migration by activating cyclooxygenase-2 and reducing peroxisome proliferator-activated receptor γ levels. Our data provide mechanistic insight as to why FABP7 is associated with a poor prognosis in MG and suggest that relative levels of DHA and AA in the tumor environment can make a profound impact on tumor growth properties. We propose that FABP7 and its fatty acid ligands may be key therapeutic targets for controlling the dissemination of MG cells within the brain.
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- © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.
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Mita, R., Beaulieu, M. J., Field, C. J., & Godbout, R. (2010). Brain fatty acid-binding protein and ω-3/ω-6 fatty acids: Mechanistic insight into the poor prognosis of malignant glioma cell migration. Journal of Biological Chemistry, 285(47), 37005-37015. http://dx.doi.org/10.1074/jbc.M110.170076
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