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

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Title
Gas6 induces cancer cell migration and epithelial-mesenchymal transition through upregulation of MAPK and Slug
Author(s)
Yunhee Lee; M Lee; Semi Kim
Bibliographic Citation
Biochemical and Biophysical Research Communications, vol. 434, no. 1, pp. 8-14
Publication Year
2013
Abstract
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.
Keyword
EMTGas6MAPKMigrationSlug
ISSN
0006-291X
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.bbrc.2013.03.082
Type
Article
Appears in Collections:
Division of Biomedical Research > Immunotherapy Research Center > 1. Journal Articles
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