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

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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1613-1622
Number of pages10
JournalCell Cycle
Volume7
Issue number11
DOIs
StatePublished - Jun 1 2008

Keywords

  • EMT
  • Epithelial-to-mesenchymal transition
  • Immortalized HaCaT keratinocytes
  • Jak2
  • Midkine
  • Notch2
  • Squamous cell carcinomas
  • Stat3
  • shRNA

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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