cSCC Migration Research Articles

Complement C3a promotes proliferation, migration and stemness in cutaneous squamous cell carcinoma.

BackgroundComplement C3 has been shown to be highly expressed in cutaneous squamous cell carcinoma (cSCC) tumour tissues and is correlated with tumour cell growth. This study aimed to investigate the mechanism of C3 in cSCC malignant transformation.MethodsC3 expression was analysed in cSCC cell lines A431, Tca8113, SCC13, HSC‐5 and HSC‐1 and in immortalized HaCaT keratinocytes. Proliferation and migration of cSCC were determined after C3a exposure. Expression of cyclin D1, cyclin E, vascular endothelial growth factor (VEGF), pro‐matrix metalloproteinase 1 (pro‐MMP1), pro‐matrix metalloproteinase 2 (pro‐MMP2), stemness factors, GSK‐3β, and β‐catenin were analyzed. Tumour growth was examined in a murine xenograft model.ResultsC3 expression was much more highly expressed in all cSCC cell lines than in HaCaT cells. C3a treatment significantly promoted cSCC cell proliferation and migration and upregulated cyclin D1, cyclin E, VEGF, pro‐MMP1 and pro‐MMP2 expression, which were impeded by the C3aR antagonist. Moreover, the expression of stemness factors Sox‐2, Nanog, Oct‐4, c‐Myc and CD‐44 was stimulated by C3a and slowed by C3aR disruption. Knockdown of Sox‐2 by siRNA transfection suppressed cell proliferation and migration, constrained VEGF secretion and inhibited pro‐MMP1 and pro‐MMP2 expression. C3a also activated the Wnt and β‐catenin pathway in cSCC cells. Disruption of C3aR expression dampened tumour growth and the expression of Wnt‐1, β‐catenin and Sox‐2 in the xenograft model.ConclusionsC3a enhanced cell proliferation, migration and stemness in cSCC, and this activity was correlated with activation of the Wnt and β‐catenin pathway.

Long non-coding RNA PICSAR decreases adhesion and promotes migration of squamous carcinoma cells by downregulating α2β1 and α5β1 integrin expression.

ABSTRACTLong non-coding RNAs (lncRNAs) regulate various cellular processes, and they have emerged as potential biomarkers and therapeutic targets in cancer. We have previously characterized the oncogenic role of lncRNA PICSAR (p38 inhibited cutaneous squamous cell carcinoma associated lincRNA) in cutaneous squamous cell carcinoma (cSCC), the most common metastatic skin cancer. In this study, we show that knockdown of PICSAR in cSCC cells upregulates expression of α2, α5 and β1 integrins, resulting in increased cell adhesion and decreased cell migration on collagen I and fibronectin. In contrast, overexpression of PICSAR in cSCC cells downregulates expression of α2, α5 and β1 integrins on cell surface, resulting in decreased cell adhesion on collagen I and fibronectin and increased cell migration. These results demonstrate a novel mechanism for regulation of the expression of collagen and fibronectin binding integrins by lncRNA PICSAR, leading to altered adhesion and migration of cSCC cells.This article has an associated First Person interview with the first author of the paper.