Targeting CD133 in the enhancement of chemosensitivity in oral squamous cell carcinoma–derived side population cancer stem cells

Yu, Cheng–Chia; Hu, Fang‐Wei; Yu, Chuan‐Hang; Chou, Ming‐Yung

doi:10.1002/hed.23975

Cited by 60 publications

(57 citation statements)

References 50 publications

(95 reference statements)

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“…However, to date, few CSC markers in OSCC have been identified (29,30). The results of the current study indicate that SOX2, KLF4 and brachyury may present clinically useful CSC markers, and their expression levels may be prognostic factors for OSCC.…”

Section: Discussionmentioning

confidence: 58%

Expression levels of SOX2, KLF4 and brachyury transcription factors are associated with metastasis and poor prognosis in oral squamous cell carcinoma

et al. 2015

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Abstract. The prognosis of oral squamous cell carcinoma (OSCC) patients is affected by tumor recurrence and metastasis, and cancer stem cells are hypothesized to be involved in these processes. Thus, the aim of the present study was to determine whether the expression levels of five stem cell-related transcription factors, sex determining region Y-box 2 (SOX2), octamer-binding transcription factor 4 (Oct4), avian myelocytomatosis viral oncogene homolog (c-Myc), Krüppel-like factor 4 (KLF4) and brachyury, are associated with metastasis and survival in OSCC. Immunohistochemistry was performed to analyze the expression of these proteins in biopsy specimens obtained from 108 OSCC patients. The results revealed that the expression of SOX2, Oct4, KLF4 and brachyury were significantly associated with lymph node metastasis (P=0.002, P=0.031, P=0.003 and P=0.007, respectively). In addition, the expression of KLF4 and brachyury were significantly associated with distant metastasis (P=0.014 and P=0.012, respectively). Furthermore, multivariate analysis revealed that SOX2 and KLF4 are predictive factors for lymph node metastasis [odds ratios (ORs), 4.526 and 4.851, respectively], and KLF4 is also a predictive factor for distant metastasis (OR, 9.607). In addition, OSCC patients with low co-expression of SOX2, KLF4 and brachyury exhibited a significantly lower disease-specific survival rate (78.6 vs. 100%; P=0.025; χ 2 =5.033) and disease-free survival rate (60.7 vs. 90.9%; P=0.015; χ 2 =5.897) when compared with OSCC patients with high co-expression of these factors. The results indicate that SOX2, KLF4 and brachyury serve important roles in tumor progression, and these transcription factors may thus represent clinically useful prognostic markers for OSCC.

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Section: Discussionmentioning

confidence: 58%

Expression levels of SOX2, KLF4 and brachyury transcription factors are associated with metastasis and poor prognosis in oral squamous cell carcinoma

et al. 2015

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“…Nevertheless, various lines of evidence suggest that CD133 is not only a surface marker but it also plays a causal role in CSC. For example, CD133 is required for the maintenance of glioblastoma stem cells [131] and confers stem-like properties and chemoresistance to other cancer cell types [133–135]. Experimental data implicated the PI3K/Akt pathway as a CD133 effector [133, 134, 136].…”

Section: Main Textmentioning

confidence: 99%

Ovarian cancer stem cells: still an elusive entity?

2017

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The cancer stem cell (CSC) model proposes that tumor development and progression are fueled and sustained by undifferentiated cancer cells, endowed with self-renewal and tumor-initiating capacity. Ovarian carcinoma, based on its biological features and clinical evolution, appears as a prototypical example of CSC-driven disease. Indeed, ovarian cancer stem cells (OCSC) would account not only for the primary tumor growth, the peritoneal spread and the relapse, but also for the development of chemoresistance, thus having profound implication for the treatment of this deadly disease. In the last decade, an increasing body of experimental evidence has supported the existence of OCSC and their pathogenic role in the disease. Nevertheless, the identification of OCSC and the definition of their phenotypical and functional traits have proven quite challenging, mainly because of the heterogeneity of the disease and of the difficulties in establishing reliable biological models. A deeper understanding of OCSC pathobiology will shed light on the mechanisms that underlie the clinical behaviour of OC. In addition, it will favour the design of innovative treatment regimens that, on one hand, would counteract the resistance to conventional chemotherapy, and, on the other, would aim at the eradication of OC through the elimination of its CSC component.

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“…Recent studies have revealed that cancer stem cells (CSCs) or termed tumor initiating cells (TICs) with tumors could contribute to tumor maintenance, metastasis, radio-resistance and chemo-resistance in a variety of cancers, including OSCC [6–11]. Moreover, the first connection of between CSCs and epithelial-mesenchymal transdifferentiation (EMT), a dynamic process in which cells lose epithelial features and gain mesenchymal properties, is demonstrated in breast cancer stem cells model [12].…”

Section: Introductionmentioning

confidence: 99%

Acquisition cancer stemness, mesenchymal transdifferentiation, and chemoresistance properties by chronic exposure of oral epithelial cells to arecoline

et al. 2016

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Oral squamous cell carcinoma (OSCC), one of the most deadliest malignancies in the world, is caused primarily by areca nut chewing in Southeast Asia. The mechanisms by which areca nut participates in OSCC tumorigenesis are not well understood. In this study, we investigated the effects of low dose long-term arecoline (10 μg/mL, 90-days), a major areca nut alkaloid, on enhancement cancer stemness of human oral epithelial (OE) cells. OE cells with chronic arecoline exposure resulted in increased ALDH1 population, CD44 positivity, stemness-related transcription factors (Oct4, Nanog, and Sox2), epithelial-mesenchymal transdifferentiation (EMT) traits, chemoresistance, migration/invasiveness/anchorage independent growth and in vivo tumor growth as compared to their untreated controls. Mechanistically, ectopic miR-145 over-expression in chronic arecoline-exposed OE (AOE) cells inhibited the cancer stemness and xenografic. In AOE cells, luciferase reporter assays further revealed that miR-145 directly targets the 3′ UTR regions of Oct4 and Sox2 and overexpression of Sox2/Oct4 effectively reversed miR-145-regulated cancer stemness-associated phenomenas. Additionally, clinical results further revealed that Sox2 and Oct4 expression was inversely correlated with miR-145 in the tissues of areca quid chewing-associated OSCC patients. This study hence attempts to provide novel insight into areca nut-induced oral carcinogenesis and new intervention for the treatment of OSCC patients, especially in areca nut users.

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Targeting CD133 in the enhancement of chemosensitivity in oral squamous cell carcinoma–derived side population cancer stem cells

Abstract: Side population cells with CSCs properties existed in OSCCs, and silencing CD133 exhibited a prominent therapeutic effect in enhancing the sensitivity of chemotherapy in OSCC through elimination of CSCs. © 2015 Wiley Periodicals, Inc. Head Neck 38: E231-E238, 2016.

Cited by 60 publications

References 50 publications

Expression levels of SOX2, KLF4 and brachyury transcription factors are associated with metastasis and poor prognosis in oral squamous cell carcinoma

Expression levels of SOX2, KLF4 and brachyury transcription factors are associated with metastasis and poor prognosis in oral squamous cell carcinoma

Ovarian cancer stem cells: still an elusive entity?

Acquisition cancer stemness, mesenchymal transdifferentiation, and chemoresistance properties by chronic exposure of oral epithelial cells to arecoline

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