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 Barone

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)265-276
Number of pages12
JournalHistochemistry and Cell Biology
Volume134
Issue number3
DOIs
Publication statusPublished - Sep 2010

    Fingerprint

Keywords

  • Epidermis
  • Epithelia
  • Keratinocyte clonal evolution
  • YAP1
  • Yes-associated protein

ASJC Scopus subject areas

  • Cell Biology
  • Histology
  • Medical Laboratory Technology
  • Molecular Biology

Cite this