Stat3 promotes directional cell migration by regulating Rac1 activity via its activator betaPIX.
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 betaPIX, 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.
Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673.
Terk Shin
TS
Teng
Baohong
B
Lin
Ed
E
Manser
Dominic Chi Hiung
DC
Ng
Xinmin
X
Cao
D000199:Actins; D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D055785:Gene Knockdown Techniques; D055786:Gene Knockout Techniques; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D064067:Rho Guanine Nucleotide Exchange Factors; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D022502:Stress Fibers / Q000378:metabolism*; D015533:Transcriptional Activation; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
D000199:Actins; C576607:Arhgef7 protein, mouse; D020662:Guanine Nucleotide Exchange Factors; D064067:Rho Guanine Nucleotide Exchange Factors; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D020830:rac1 GTP-Binding Protein