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

International Journal of Molecular Sciences

Roberta Lotti²  Elisabetta Palazzo²  Tiziana Petrachi²  Katiuscia Dallaglio²  Annalisa Saltari²  Francesca Truzzi²  Marika Quadri²  Mario Puviani³  Antonino Maiorana¹  Alessandra Marconi²  Carlo Pincelli² 

[1] Department of Laboratories and Pathologic Anatomy, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124 Modena, Italy;Laboratory of Cutaneous Biology, Department of Surgical, Medical, Dental and Morphological Sciences, University of Modena and Reggio Emilia, via del Pozzo 71, 41124 Modena, Italy;Ospedale Civile di Sassuolo, Via Francesco Ruini 2, 41049 Sassuolo (MO), Italy;

关键词: squamous cell carcinoma;    stem cells;    β₁-integrin;    tumor formation;    survivin;    rapidly adhering cells;    skin;    tumorigenesis;    differentiation;   

DOI  :  10.3390/ijms17010089

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2016 by the authors; licensee MDPI, Basel, Switzerland.