Journal
JOURNAL OF CELL SCIENCE
Volume 122, Issue 22, Pages 4150-4159Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.057109
Keywords
Actin; beta PIX; Cell migration; Rac1; Stat3
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Funding
- Agency for Science, Technology and Research of Singapore
- GSK-IMCB Singapore
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Stat3 is a member of the signal transducer and activator of transcription family, which is important for cytokine signaling as well as for a number of cellular processes including cell proliferation, anti-apoptosis and immune responses. In recent years, evidence has emerged suggesting that Stat3 also participates in cell invasion and motility. However, how Stat3 regulates these processes remains poorly understood. Here, we find that loss of Stat3 expression in mouse embryonic fibroblasts leads to an elevation of Rac1 activity, which promotes a random mode of migration by reducing directional persistence and formation of actin stress fibers. Through rescue experiments, we demonstrate that Stat3 can regulate the activation of Rac1 to mediate persistent directional migration and that this function is not dependent on Stat3 transcriptional activity. We find that Stat3 binds to beta PIX, a Rac1 activator, and that this interaction could represent a mechanism by which cytoplasmic Stat3 regulates Rac1 activity to modulate the organization of actin cytoskeleton and directional migration.
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