TY - JOUR AB - Oral squamous cell carcinoma (OSCC) is an extremely aggressive disease associated with a poor prognosis. Previous studies have established that cancer stem cells (CSCs) actively participate in OSCC development, progression and resistance to conventional treatments. Furthermore, CSCs frequently exhibit a deregulated expression of normal stem cell signalling pathways, thereby acquiring their distinctive abilities, of which self-renewal is an example. In this study, we examined the effects of GLI3 knockdown in OSCC, as well as the differentially expressed genes in CSC-like cells (CSCLCs) expressing high (CD44high) or low (CD44low) levels of CD44. The prognostic value of GLI3 in OSCC was also evaluated. The OSCC cell lines were sorted based on CD44 expression; gene expression was evaluated using a PCR array. Following this, we examined the effects of GLI3 knockdown on CD44 and ESA expression, colony and sphere formation capability, stem-related gene expression, proliferation and invasion. The overexpression of genes related to the Notch, transforming growth factor (TGF)β, FGF, Hedgehog, Wnt and pluripotency maintenance pathways was observed in the CD44high cells. GLI3 knockdown was associated with a significant decrease in different CSCLC fractions, spheres and colonies in addition to the downregulation of the CD44, Octamer-binding transcription factor 4 (OCT4; also known as POU5F1) and BMI1 genes. This downregulation was accompanied by an increase in the expression of the Involucrin (IVL) and S100A9 genes. Cellular proliferation and invasion were inhibited following GLI3 knockdown. In OSCC samples, a high GLI3 expression was associated with tumour size but not with prognosis. On the whole, the findings of this study demonstrate for the first time, at least to the best of our knowledge, that GLI3 contributes to OSCC stemness and malignant behaviour. These findings suggest the potential for the development of novel therapies, either in isolation or in combination with other drugs, based on CSCs in OSCC. AD - Postgraduate Program in Biophotonics Applied to Health Sciences, Nove de Julho University (UNINOVE), São Paulo 01504000, Brazil Department of Oral Pathology, School of Dentistry, University of São Paulo, São Paulo 05508000, Brazil Department of Biological Sciences, Bauru School of Dentistry, Bauru 17012901, Brazil Department of Head and Neck Surgery, School of Medicine, University of São Paulo, São Paulo 03178200, Brazil School of Public Health, University of São Paulo, São Paulo 03178200, Brazil Department of Head and Neck Surgery, Barretos Cancer Hospital, Barretos 014784400, Brazil Department of Molecular Biology, School of Medicine of São José do Rio Preto, São José do Rio Preto 15090000, Brazil AU - Rodrigues,Maria Fernanda ,Setúbal Destro AU - Miguita,Lucyene AU - De Andrade,Nathália ,Paiva AU - Heguedusch,Daniele AU - Rodini,Camila ,Oliveira AU - Moyses,Raquel ,Ajub AU - Toporcov,Tatiana ,Natasha AU - Gama,Ricardo ,Ribeiro AU - Tajara,Eloiza ,Elena AU - Nunes,Fabio ,Daumas DA - 2018/12/01 DO - 10.3892/ijo.2018.4572 EP - 2472 IS - 6 JO - Int J Oncol KW - oral squamous cell carcinoma cancer stem cell-like cells stem cell signaling pathways CD44 GLI3 PY - 2018 SN - 1019-6439 1791-2423 SP - 2458 ST - GLI3 knockdown decreases stemness, cell proliferation and invasion in oral squamous cell carcinoma T2 - International Journal of Oncology TI - GLI3 knockdown decreases stemness, cell proliferation and invasion in oral squamous cell carcinoma UR - https://doi.org/10.3892/ijo.2018.4572 VL - 53 ER -