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.
Copyright © 2013 Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Activating Transcription Factor 2 / metabolism
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Cell Line, Tumor
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Cell Movement
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Down-Regulation / genetics
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Epithelial-Mesenchymal Transition / physiology*
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HEK293 Cells
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Humans
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Intercellular Signaling Peptides and Proteins / physiology*
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JNK Mitogen-Activated Protein Kinases / metabolism
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MAP Kinase Signaling System / physiology*
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Male
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Neoplasm Invasiveness / pathology*
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Neoplasm Invasiveness / physiopathology
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Phosphorylation
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Snail Family Transcription Factors
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Transcription Factors / antagonists & inhibitors
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Transcription Factors / biosynthesis*
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Transcription Factors / genetics
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Up-Regulation / genetics
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Up-Regulation / physiology*
Substances
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ATF2 protein, human
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Activating Transcription Factor 2
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Intercellular Signaling Peptides and Proteins
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SNAI1 protein, human
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Snail Family Transcription Factors
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Transcription Factors
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growth arrest-specific protein 6
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JNK Mitogen-Activated Protein Kinases