Regulation of tumorigenesis in oral epithelial cells by defined reprogramming factors Oct4 and Sox2

Cai, Jinghua; Li, Xinming; Sun, Minglei; Lam, Alfred King‐Yin; Qiao, Bin; Qiu, Weimin

doi:10.3892/or.2016.4851

Cited by 16 publications

(16 citation statements)

References 26 publications

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“…Arnold et al [27] reported that epithelial adult stem cells expressing SOX2 may be residual stem niches that originate from embryonic SOX2-positive tissue progenitors. Cai et al [28] investigated the roles of OCT4 and SOX2 in the reprogramming of oral cancer stem cells. They immortalized oral epithelial cells by lentiviral transduction and found that double-transduced OCT4 + SOX2 + cells were able to trigger tumor formation in immunodeficient mice; however, single-transduced OCT4 + or SOX2 + cells did not show tumorigenic capacity.…”

Section: Discussionmentioning

confidence: 99%

SOX2 Expression Is an Independent Predictor of Oral Cancer Progression

Vicente

Molino

Rodrigo

et al. 2019

JCM

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Potentially malignant oral lesions, mainly leukoplakia, are common. Malignant transformation varies widely, even in the absence of histological features such as dysplasia. Hence, there is a need for novel biomarker-based systems to more accurately predict the risk of cancer progression. The pluripotency transcription factor SOX2 is frequently overexpressed in cancers, including oral squamous cell carcinoma (OSCC), thereby providing a link between malignancy and stemness. This study investigates the clinical relevance of SOX2 protein expression in early stages of oral carcinogenesis as a cancer risk biomarker, and also its impact on prognosis and disease outcome at late stages of OSCC progression. SOX2 expression was evaluated by immunohistochemistry in 55 patients with oral epithelial dysplasia, and in 125 patients with OSCC, and correlated with clinicopathological data and outcomes. Nuclear SOX2 expression was detected in four (7%) cases of oral epithelial dysplasia, using a cut-off of 10% stained nuclei, and in 16 (29%) cases when any positive nuclei was evaluated. Univariate analysis showed that SOX2 expression and histopathological grading were significantly associated with oral cancer risk; and both were found to be significant independent predictors in the multivariate analysis. Nuclear SOX2 expression was also found in 49 (39%) OSCC cases, was more frequent in early tumor stages and N0 cases, and was associated with a better survival. In conclusion, SOX2 expression emerges as an independent predictor of oral cancer risk in patients with oral leukoplakia. These findings underscore the relevant role of SOX2 in early oral tumorigenesis rather than in tumor progression.

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Section: Discussionmentioning

confidence: 99%

SOX2 Expression Is an Independent Predictor of Oral Cancer Progression

Vicente

Molino

Rodrigo

et al. 2019

JCM

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“…It was also shown that the BMI1 gene actively participated in the acquisition of resistance, which was influenced by IL6 ( 74 ). POU5F1 ( OCT4 ) also plays an important role in CSC and its overexpression, increases the capacity for tumour initiation, tumour sphere formation, invasion and the acquisition of the EMT phenotype in OSCC cells lines ( 75 , 76 ).…”

Section: Discussionmentioning

confidence: 99%

GLI3 knockdown decreases stemness, cell proliferation and invasion in oral squamous cell carcinoma

Rodrigues

Miguita²,

Andrade³

et al. 2018

Int J Oncol

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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.

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“…In addition, it has been reported that SOX-2 plays an important role in the maintenance of self-renewal of CSCs [31]. Knockdown of SOX-2 and Oct4 reduced the tumour size in oral cancer in immunodeficient mice [32]. Furthermore, SOX-2 was found positive in 159 (55%) of 290 gastric cancers [23].…”

Section: Identification Of Cscs In Crc (Table 1)mentioning

confidence: 99%

The Identifications and Clinical Implications of Cancer Stem Cells in Colorectal Cancer

Wahab

Islam

Gopalan

2017

Clinical Colorectal Cancer

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Cancer stem cells (CSCs) are cancer cells that are responsible for initiation, progression, metastasis, and recurrence in cancer. The aim of this review was to analyze the markers for identifying of CSCs in colorectal carcinoma, as well as the prognostic and therapeutic implications of these markers in the cancer. CSCs are insensitive to the current drug regimens. In colorectal carcinoma, markers, including Nanog, Oct-4, SOX-2, Lgr-5, CD133, CD24, CD29, ALDH1, EpCAM, CD44, CD166, and CD26, are commonly used for the identification and isolation of CSCs. In addition, ALDH1, CD24, CD44, CD133, CD166, EpCAM, Lgr-5, Nanog, and SOX-2 could have clinical roles in predicting pathological stages, cancer recurrence, therapy resistance, and patients' survival in patients with colorectal carcinoma. In light of the current knowledge of CSCs in colorectal carcinoma, novel potential therapeutic strategies, such as development of monoclonal antibodies or immunotoxins and targeting various cell surface molecules in colorectal CSCs and/or components of signaling pathways, have been developed. This could open new opportunities for the better management of patients with colorectal carcinoma.

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Regulation of tumorigenesis in oral epithelial cells by defined reprogramming factors Oct4 and Sox2

Cited by 16 publications

References 26 publications

SOX2 Expression Is an Independent Predictor of Oral Cancer Progression

SOX2 Expression Is an Independent Predictor of Oral Cancer Progression

GLI3 knockdown decreases stemness, cell proliferation and invasion in oral squamous cell carcinoma

The Identifications and Clinical Implications of Cancer Stem Cells in Colorectal Cancer

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