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Reports

Midkine induces epithelial-mesenchymal transition through Notch2/Jak2-Stat3 signaling in human keratinocytes

Yiping Huang, Mohammad Obaidul Hoque, Feng Wu, Barry Trink, David Sidransky and Edward A. Ratovitski

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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.

Authors

Yiping Huang

Johns Hopkins University School of Medicine; Baltimore, MD

Mohammad Obaidul Hoque

Johns Hopkins University School of Medicine; Baltimore, MD

Feng Wu

Johns Hopkins University School of Medicine; Baltimore, MD

Barry Trink

Johns Hopkins University School of Medicine; Baltimore, MD

David Sidransky

Johns Hopkins University School of Medicine; Baltimore, MD

Edward A. Ratovitski

Johns Hopkins University School of Medicine; Baltimore, MD

Purchase article for $19

Subscribe to this journal for $129/year