Midkine induces epithelial-mesenchymal transition through Notch2/Jak2-Stat3 signaling in human keratinocytes
Copyright policy )Midkine induces epithelial-mesenchymal transition through Notch2/Jak2-Stat3 signaling in human keratinocytes
Epithelial-to-mesenchymal transition (EMT) underlies cell plasticity and embryonic development and is frequently observed in advanced tumorigenesis. We demonstrated that midkine (MK), a retinoic acid-inducible heparin-binding mitogen, promotes EMT in immortalized HaCaT keratinocytes. We showed that MK binds to the Notch2 receptor in HaCaT keratinocytes. We further found that MK activates Notch2 signaling leading to protein/protein interactions between Hes1 and Jak2/Stat3 intermediates. We thus suggest that MK-induced cross talk of Notch2/Jak2/Stat3 signaling pathways can regulate cell plasticity and motility contributing to the EMT and later stages of tumorigenesis.
- Johns Hopkins University United States
- Johns Hopkins Medicine United States
- Johns Hopkins University School of Medicine United States
Keratinocytes, STAT3 Transcription Factor, Reverse Transcriptase Polymerase Chain Reaction, Gene Expression Profiling, Immunoblotting, Midkine, Cell Differentiation, Enzyme-Linked Immunosorbent Assay, Epithelial Cells, Janus Kinase 2, Mesoderm, Microscopy, Fluorescence, Neoplasms, Two-Hybrid System Techniques, Cytokines, Humans, Receptor, Notch2, DNA Primers, Signal Transduction
Keratinocytes, STAT3 Transcription Factor, Reverse Transcriptase Polymerase Chain Reaction, Gene Expression Profiling, Immunoblotting, Midkine, Cell Differentiation, Enzyme-Linked Immunosorbent Assay, Epithelial Cells, Janus Kinase 2, Mesoderm, Microscopy, Fluorescence, Neoplasms, Two-Hybrid System Techniques, Cytokines, Humans, Receptor, Notch2, DNA Primers, Signal Transduction
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