Survivin modulates squamous cell carcinoma-derived stem-like cell proliferation, viability and tumor formation in vivo

Roberta Lotti, Elisabetta Palazzo, Tiziana Petrachi, Katiuscia Dallaglio, Annalisa Saltari, Francesca Truzzi, Marika Quadri, Mario Puviani, Antonino Maiorana, Alessandra Marconi, Carlo Pincelli

Research output: Contribution to journalArticlepeer-review

Abstract

Squamous Cell Carcinoma-derived Stem-like Cells (SCC-SC) originate from alterations in keratinocyte stem cells (KSC) gene expression and sustain tumor development, invasion and recurrence. Since survivin, a KSC marker, is highly expressed in SCC-SC, we evaluate its role in SCC-SC cell growth and SCC models. Survivin silencing by siRNA decreases clonal growth of SCC keratinocytes and viability of total, rapidly adhering (RAD) and non-RAD (NRAD) cells from primary SCC. Similarly, survivin silencing reduces the expression of stem cell markers (OCT4, NOTCH1, CD133, β1-integrin), while it increases the level of differentiation markers (K10, involucrin). Moreover, survivin silencing improves the malignant phenotype of SCC 3D-reconstruct, as demonstrated by reduced epidermal thickness, lower Ki-67 positive cell number, and decreased expression of MMP9 and psoriasin. Furthermore, survivin depletion by siRNA in RasG12V-IκBα-derived tumors leads to smaller tumor formation characterized by lower mitotic index and reduced expression of the tumor-associated marker HIF1α, VEGF and CD51. Therefore, our results indicate survivin as a key gene in regulating SCC cancer stem cell formation and cSCC development.

Original languageEnglish
Article number89
JournalInternational Journal of Molecular Sciences
Volume17
Issue number1
DOIs
Publication statusPublished - Jan 12 2016

Keywords

  • Differentiation
  • Rapidly adhering cells
  • Skin
  • Squamous cell carcinoma
  • Stem cells
  • Survivin
  • Tumor formation
  • Tumorigenesis
  • β-integrin

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Spectroscopy
  • Inorganic Chemistry
  • Catalysis
  • Molecular Biology
  • Computer Science Applications

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