Histochemistry and Cell Biology

, Volume 134, Issue 3, pp 265–276 | Cite as

Overexpression of YAP1 induces immortalization of normal human keratinocytes by blocking clonal evolution

  • Irene D’Addario
  • Claudia Abbruzzese
  • Marco Lo Iacono
  • Massimo Teson
  • Osvaldo Golisano
  • Virginia BaroneEmail author
Original Paper


YAP1 is a transcriptional co-activator able to bind several transcription factors. YAP1 was termed a candidate oncogene after it was shown to be in human chromosome 11q22 amplicon; besides the genomic amplification, several experiments indicated that it has oncogenic function. However, YAP1 was also reported to be a tumor suppressor as its gene locus is deleted in some breast cancers. To clarify the role of this protein in the physiology of rapidly renewal cells, we investigated YAP1 in human keratinocytes. Here, we show that YAP1 overexpression in primary human keratinocytes blocks clonal evolution and induces cell immortalization, but not malignant transformation. YAP1 overexpression led to an increase in cell proliferation, colony forming efficiency and holoclone percentage. Cells escaped from senescence, immortalized but still remained unable to grow in soft agar or express mesenchymal markers, suggesting that YAP1 overexpression is not sufficient to promote a complete epithelial–mesenchymal transition and tumorigenic transformation. Protein analysis showed an increase in epithelial proliferation markers and a decrease in epithelial differentiation markers. The expression of LEKTI, a late differentiation marker, dramatically dropped to undetectable levels. Taken together, these data suggest that YAP1-overexpressing keratinocytes are maintained in the proliferative compartment.


YAP1 Yes-associated protein Keratinocyte clonal evolution Epidermis Epithelia 



This work was supported by the Italian Ministero della Sanità.

Conflict of interest



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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Irene D’Addario
    • 1
  • Claudia Abbruzzese
    • 1
  • Marco Lo Iacono
    • 2
  • Massimo Teson
    • 3
  • Osvaldo Golisano
    • 4
  • Virginia Barone
    • 1
    • 5
    Email author
  1. 1.Laboratory of Tissue Engineering and Cutaneous PhysiopathologyIstituto Dermopatico dell’Immacolata, IRCCSRomeItaly
  2. 2.Department of Biological and Clinical SciencesUniversity of TurinTurinItaly
  3. 3.Laboratory of Molecular and Cell BiologyIstituto Dermopatico dell’Immacolata, IRCCSRomeItaly
  4. 4.IDI Farmaceutici SPAPomeziaItaly
  5. 5.Molecular Medicine Section, Department of NeuroscienceUniversity of SienaSienaItaly

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