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Biochem Biophys Res Commun. 2013 Apr 26;434(1):8-14. doi: 10.1016/j.bbrc.2013.03.082. Epub 2013 Apr 6.

Gas6 induces cancer cell migration and epithelial-mesenchymal transition through upregulation of MAPK and Slug.

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Department of Chemistry, Korea Advanced Institute of Science and Technology, Daejeon, South Korea.


Binding of Gas6 to Axl (Gas6/Axl axis) alters cellular functions, including migration, invasion, proliferation, and survival. However, the molecular mechanisms underlying Gas6-mediated cell migration remain poorly understood. In this study, we found that Gas6 induced the activation of JNK and ERK1/2 signaling in cancer cells expressing Axl, resulting in the phosphorylation of activator protein-1 (AP-1) transcription factors c-Jun and ATF-2, and induction of Slug. Depletion of c-Jun or ATF-2 by siRNA attenuated the Gas6-induced expression of Slug. Slug expression was required for cell migration and E-cadherin reduction/vimentin induction induced by Gas6. These results suggest that Gas6 induced cell migration via Slug upregulation in JNK- and ERK1/2-dependent mechanisms. These data provide an important insight into the molecular mechanisms mediating Gas6-induced cell migration.

[Indexed for MEDLINE]

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