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

Author:
Lee, Yunhee, Lee, Mira, Kim, Semi
Source:
Biochemical and biophysical research communications 2013 v.434 pp. 8-14
ISSN:
0006-291X
Subject:
cell movement, mitogen-activated protein kinase, neoplasm cells, phosphorylation, small interfering RNA, transcription factors, vimentin
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.
Agid:
897351