Survivin Modulates Squamous Cell Carcinoma-Derived Stem-Like Cell Proliferation, Viability and Tumor Formation in Vivo

International Journal of Molecular Sciences
R LottiC Pincelli

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 Ras(G12V)-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.

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Citations

Jun 28, 2016·International Journal of Molecular Sciences·Wilhelm Bloch
Mar 11, 2018·Nature Communications·Paola ArcidiaconoAnissa Chikh
May 8, 2019·International Journal of Molecular Sciences·Stephen J GoldieCharbel Darido
May 26, 2017·Cellular & Molecular Biology Letters·Zakir KhanPrakash Singh Bisen
Jul 25, 2019·International Journal of Molecular Sciences·Elisabetta PalazzoMaria I Morasso

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Methods Mentioned

BETA
transfection
biopsies
FCS

Software Mentioned

ImageJ

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