title: Gas6 induces cancer cell migration and epithelial-mesenchymal transition through upregulation of MAPK and Slug.
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.
authors.affiliation: Department of Chemistry, Korea Advanced Institute of Science and Technology, Daejeon, South Korea.
authors.forename: Yunhee
authors.initials: Y
authors.lastname: Lee
authors.forename: Mira
authors.initials: M
authors.lastname: Lee
authors.forename: Semi
authors.initials: S
authors.lastname: Kim
mesh_terms: D051698:Activating Transcription Factor 2 / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D015536:Down-Regulation / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D009361:Neoplasm Invasiveness / Q000473:pathology* / Q000503:physiopathology; D010766:Phosphorylation; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics / Q000502:physiology*; D000099255:Growth Arrest-Specific Protein 6
chemical_list: D051698:Activating Transcription Factor 2; D036341:Intercellular Signaling Peptides and Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D000099255:Growth Arrest-Specific Protein 6; C497105:ATF2 protein, human; C000604407:SNAI1 protein, human