Midkine/P63 axis in regulation of epithelial-mesenchymal transition

Yiping Huang, Edward A. Ratovitski

Research output: Chapter in Book/Report/Conference proceedingChapter


The heparin-binding growth and differentiation factor/mitogen, midkine, was shown to play a critical role in embryonic development, prenatal differentiation and tumorigenesis, specifically as a regulator of the epithelial-mesenchymal transition/transdifferentiation. Along with other growth factors/mitogens, midkine was reported to activate the key signaling pathways leading to ability tumor cells to migrate and support cell invasiveness. Midkine was also found to act as an anti-apoptotic and pro-survival factor. In this report, we showed the interplay between the midkine- and p63-dependent signaling pathways potentially leading to the epithelial-mesenchymal transdifferentation. We showed that the midkine transcription is regulated by p63 supported by promoter/reporter and chromatin immunoprecipitation assays. We further showed that midkine induces expression of ΔNp63 isotypes potentially leading to cell migration and cell invasiveness through the Stat3-dependent activation of the ΔNp63 promoter activity. Overall, we suggest a novel feedback loop mechanism underlying crosstalk between midkine and p63 pathways during epithelial-mesenchymal transdifferentation.

Original languageEnglish (US)
Title of host publicationMidkine
Subtitle of host publicationFrom Embryogenesis to Pathogenesis and Therapy
PublisherSpringer Netherlands
Number of pages12
ISBN (Electronic)9789400742345
ISBN (Print)9400742339, 9789400742338
StatePublished - Nov 1 2012
Externally publishedYes


  • Epithelial-mesenchymal transdifferentation
  • Midkine
  • Squamous cell carcinoma
  • Transcription
  • Tumor protein 63

ASJC Scopus subject areas

  • General Medicine


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