A JAK/STAT invasion

Asignalingpathway that is critical in fly eggs might be a key to understanding cancer cell metastasis, according to Debra Silver and Denise Montell (Johns Hopkins School of Medicine, Baltimore, MD). They have found that activation of the JAK/STAT signaling pathway triggers the migration of border cells, which start off at the anterior end of the egg chamber, travel in between the nurse cells, and end up at the anterior end of the oocyte. Once they settle down, the border cells provide patterning information and help build an anterior eggshell structure that aids in fertilization.

In mammals, the same pathway is triggered by certain cytokines. Binding induces receptor dimerization, cross-phosphorylation of and by the receptor-bound JAK kinases, and docking and activation of STAT transcription factors. The pathway is constitutively activated in many human cancers, and Montell believes that the consequence may be increased migration, in addition to the previously noted effects on survival and proliferation.

This may be especially pertinent for the many cancers that are derived from normally stationary epithelial cells. In the flies, says Montell, “we're studying the conversion of epithelial cells to migratory cells, and this is something that characterizes metastasis.” Experiments are underway to test whether manipulation of the JAK/STAT pathway in ovarian carcinoma cells affects the cells' motility. ▪

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