Survivin identifies keratinocyte stem cells and is downregulated by anti-β1 integrin during anoikis

Alessandra Marconi, Katiuscia Dallaglio, Roberta Lotti, Cristina Vaschieri, Francesca Truzzi, Fabrizio Fantini, Carlo Pincelli

Research output: Contribution to journalArticlepeer-review

Abstract

Survivin belongs to the family of inhibitor of apoptosis proteins and is involved in regulation of cell death as well as cell division. Here, we show that wild-type (WT) survivin is expressed in a subpopulation of basal keratinocytes in normal human skin at the cytoplasmic level. WT survivin is highly expressed in keratinocyte stem cells (KSCs), whereas its mRNA level decreases in transit amplifying (TA) cells and disappears in postmitotic (PM) cells. Likewise, WT survivin protein is expressed in KSCs, almost undetectable in TA cells, and absent in PM cells. Real time polymerase chain reaction demonstrates that the putative antiapoptotic isoforms survivin-2B and survivin-ΔEx3 are expressed at the highest levels in KSCs, whereas they tend to decrease in TA cells and disappear in PM cells. On the contrary, the putative proapoptotic variants of survivin, survivin-3B, and survivin-2α tend to be high in PM and TA cells and are almost absent in KSCs. By confocal microscopy, survivin is predominantly expressed at the nuclear level in KSCs, which proliferate significantly better than TA cells, which, in turn, express mostly cytosolic WT survivin. Blocking β1 integrin signal downregulates WT survivin mRNA and protein expression and induces apoptosis (anoikis) in KSCs. On the other hand, inhibition of β1 integrin upregulates mRNA expression of survivin-2α. Taken together, these results indicate that survivin identifies human KSCs. Expression of nuclear survivin could reflect the different behavior between KSCs in vitro and in vivo, in terms of proliferation. Finally, survivin could be part of the "niche" protection by preventing anoikis in KSCs.

Original languageEnglish
Pages (from-to)149-155
Number of pages7
JournalStem Cells
Volume25
Issue number1
DOIs
Publication statusPublished - Jan 2007

Keywords

  • Anoikis
  • Keratinocytes
  • Stem cells
  • Survivin

ASJC Scopus subject areas

  • Cell Biology

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