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 journalArticle

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

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stem cells
Cell proliferation
Stem cells
viability
Tumors
Squamous Cell Carcinoma
Cell Survival
Stem Cells
tumors
cancer
Cell Proliferation
markers
Keratinocytes
Small Interfering RNA
Neoplasms
Differentiation Antigens
Cell growth
Gene expression
Integrins
Vascular Endothelial Growth Factor A

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

Cite this

Survivin modulates squamous cell carcinoma-derived stem-like cell proliferation, viability and tumor formation in vivo. / Lotti, Roberta; Palazzo, Elisabetta; Petrachi, Tiziana; Dallaglio, Katiuscia; Saltari, Annalisa; Truzzi, Francesca; Quadri, Marika; Puviani, Mario; Maiorana, Antonino; Marconi, Alessandra; Pincelli, Carlo.

In: International Journal of Molecular Sciences, Vol. 17, No. 1, 89, 12.01.2016.

Research output: Contribution to journalArticle

Lotti, R, Palazzo, E, Petrachi, T, Dallaglio, K, Saltari, A, Truzzi, F, Quadri, M, Puviani, M, Maiorana, A, Marconi, A & Pincelli, C 2016, 'Survivin modulates squamous cell carcinoma-derived stem-like cell proliferation, viability and tumor formation in vivo', International Journal of Molecular Sciences, vol. 17, no. 1, 89. https://doi.org/10.3390/ijms17010089
Lotti, Roberta ; Palazzo, Elisabetta ; Petrachi, Tiziana ; Dallaglio, Katiuscia ; Saltari, Annalisa ; Truzzi, Francesca ; Quadri, Marika ; Puviani, Mario ; Maiorana, Antonino ; Marconi, Alessandra ; Pincelli, Carlo. / Survivin modulates squamous cell carcinoma-derived stem-like cell proliferation, viability and tumor formation in vivo. In: International Journal of Molecular Sciences. 2016 ; Vol. 17, No. 1.
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