Inhibition of tumorigenicity and enhancement of radiochemosensitivity in head and neck squamous cell cancer-derived ALDH1-positive cells by knockdown of Bmi-1

Chen, Yu‐Chih; Chang, Charn Jung; Hsu, Han Shui; Chen, Yi Wei; Tai, Lung Kuo; Tseng, Ling Ming; Chiou, Guang-Yuh; Chang, Shih Ching; Chiou, Shih Hwa; Lo, Wen-Liang

doi:10.1016/j.oraloncology.2009.11.007

Cited by 106 publications

(115 citation statements)

References 28 publications

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“…Recently, ALDH1 has been shown to be a putative marker of cancer stem cells (CSC) in breast cancer, hepatoma, colon cancer, and HNSCC (5,6). Importantly, CD44/ALDH1-coexpressing HNSCC cells display high tumorigenic and radioresistant properties and may serve as a reservoir for developing tumors and metastasis (8).…”

Section: Introductionmentioning

confidence: 99%

Cucurbitacin I Suppressed Stem-Like Property and Enhanced Radiation-Induced Apoptosis in Head and Neck Squamous Carcinoma–Derived CD44+ALDH1+ Cells

Chen

Huang

et al. 2010

Molecular Cancer Therapeutics

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Head and neck squamous cell carcinoma (HNSCC) is a prevalent cancer worldwide. Signal transducers and activators of transcription 3 (STAT3) signaling is reported to promote tumor malignancy and recurrence in HNSCC. Cucurbitacins, triterpenoid derivatives, are strong STAT3 inhibitors with anticancer properties. Recent studies have shown aldehyde dehydrogenase 1 (ALDH1) to be a marker of cancer stem cells (CSC) in HNSCC. The aim of this study was to investigate the therapeutic effect of cucurbitacin I in HNSCC-derived CSCs. Using immunohistochemical analysis, we firstly showed that CD44, ALDH1, and phosphorylated STAT3 (p-STAT3) were higher in high-grade HNSCCs, and that triple positivity for CD44/ALDH1/p-STAT3 indicated a worse prognosis for HNSCC patients. Secondly, CD44

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Section: Introductionmentioning

confidence: 99%

Cucurbitacin I Suppressed Stem-Like Property and Enhanced Radiation-Induced Apoptosis in Head and Neck Squamous Carcinoma–Derived CD44+ALDH1+ Cells

Chen

Huang

et al. 2010

Molecular Cancer Therapeutics

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123

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“…Bmi1 and CD44 knockdowns have led to an improve ment of CSCs chemosensitivity in HNSCC. In particular, knockdown of CD44 increased the sensitivity of HNSCC cells to cisplatin, underlying the crucial of CSCs in the response to chemotherapy [32] . Concerning Bmi1, a stemcellrelated gene, which participates in the self renewal of hematopoietic and neuronal stem cells, and has been implicated in the tumorigenesis of various mali gnancies the experiment showed that that knockdown Krishnamurthy and al showed that targeting CSCs either directly or via their niche could lead to a more durable response in HNSCC, hence the emergence of a new concept using both conventional chemotherapy and CSC targeted therapy [36] .…”

Section: Cscs and Therapeutic Resistancementioning

confidence: 99%

“…Moreover, Chen et al [32] focused on the Snail superfamily of zincfinger transcription factors, implicated in the regulation of EMT during embryonic development. The importance of SNAI1 in the growth of cancer cells and their metastatic potential has been shown in various malignancies [34] .…”

Section: Refmentioning

confidence: 99%

“…The importance of SNAI1 in the growth of cancer cells and their metastatic potential has been shown in various malignancies [34] . Chen et al [32] found that the endogenous coexpression of ALDH1+ and Snail resulted in decreased ALDH1 expression, inhibition of CSClike properties, and dec reased tumorigenesis in ALDH1+ CD44+ cells. By regulating the EMT, Snail is a key factor in maintaining CSC properties, and could be used as a therapeutic measure for the treatment of HNSCC.…”

Section: Refmentioning

confidence: 99%

“…By regulating the EMT, Snail is a key factor in maintaining CSC properties, and could be used as a therapeutic measure for the treatment of HNSCC. Besides, Snail small interfering RNA could reduce resistance to chemo radiotherapy in ALDH1+ cells [32] . Ultimately, the expre ssion of drug efflux pumps by CSCs, another mechanism of chemo resistance remains to be explored in HNSCC.…”

Section: Refmentioning

confidence: 99%

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Targeting head and neck tumoral stem cells: From biological aspects to therapeutic perspectives

Méry¹

2016

WJSC

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Head and neck squamous cell cancer (HNSCC) is the sixth most common cancer in the world. Effective therapeutic modalities such as surgery, radiation, chemotherapy and combinations of each are used in the management of the disease. In most cases, treatment fails to obtain total cancer cure. In recent years, it appears that one of the key determinants of treatment failure may be the presence of cancer stem cells (CSCs) that escape currently available therapies. CSCs form a small portion of the total tumor burden but may play a disproportionately important role in determining outcomes. CSCs have stem features such as self-renewal, high migration capacity, drug resistance, high proliferation abilities. A large body of evidence points to the fact that CSCs are particularly resistant to radiotherapy and chemotherapy. In HNSCC, CSCs have been increasingly shown to have an integral role in tumor initiation, disease progression, metastasis and treatment resistance. In the light of such observations, the present review summarizes biological characteristics of CSCs in HNSCC, outlines targeted strategies for the successful eradication of CSCs in HNSCC including targeting the self-renewal controlling pathways, blocking epithelial mesenchymal transition, niche targeting, immunotherapy approaches and highlights the need to better understand CSCs biology for new treatments modalities.

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Expression of ABCG2 and Bmi‐1 in oral potentially malignant lesions and oral squamous cell carcinoma

et al. 2014

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Early diagnosis is vital for effective treatment of oral squamous cell carcinoma (OSCC). The optimal time for clinical intervention is prior to malignancy when patients present with oral potentially malignant lesions such as leukoplakia or erythroplakia. Transformation rates for oral dysplasia vary greatly and more rigorous methods are needed to predict the malignant potential of oral lesions. We hypothesized that the expression of two putative stem cell markers, ABCG2 and Bmi-1, would correlate with disease severity for non diseased, potentially malignant and OSCC specimens and cell lines derived from an equivalent range of tissues. We compared immunoreactive protein and relative gene expression of ABCG2 and Bmi-1 in eight cell lines derived from source tissues ranging in disease severity from normal (OKF6-TERT2) through mild and moderate/severe dysplasia (DOK, POE-9n) to OSCC (PE/CA-PJ15, SCC04, SCC25, SCC09, SCC15). We also analyzed immunoreactive protein expression of ABCG2 and Bmi-1 in 189 tissue samples with the same range of disease severity. A trend between oral lesion severity to ABCG2 and Bmi-1 immunostain intensity was observed. Flow cytometry of oral cell lines confirmed this trend and gave good correlation with RT-PCR results for ABCG2 (r = 0.919, P = 0.001; Pearson) but not Bmi-1 (r = −0.311). The results provide evidence of increased density of ABCG2 and Bmi-1-positive populations in malignant and oral potentially malignant lesions and derived cell lines, but that intragroup variability within IHC, flow cytometry, and RT-PCR results compromise the diagnostic potential of these techniques for discriminating oral dysplasia from normal tissue or OSCC.

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Inhibition of tumorigenicity and enhancement of radiochemosensitivity in head and neck squamous cell cancer-derived ALDH1-positive cells by knockdown of Bmi-1

Cited by 106 publications

References 28 publications

Cucurbitacin I Suppressed Stem-Like Property and Enhanced Radiation-Induced Apoptosis in Head and Neck Squamous Carcinoma–Derived CD44+ALDH1+ Cells

Cucurbitacin I Suppressed Stem-Like Property and Enhanced Radiation-Induced Apoptosis in Head and Neck Squamous Carcinoma–Derived CD44+ALDH1+ Cells

Targeting head and neck tumoral stem cells: From biological aspects to therapeutic perspectives

Expression of ABCG2 and Bmi‐1 in oral potentially malignant lesions and oral squamous cell carcinoma

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