Overexpression of NBS1 induces epithelial–mesenchymal transition and co-expression of NBS1 and Snail predicts metastasis of head and neck cancer

Mh, Yang; Sy, Chang; Sh, Chiou; Cj, Liu; Cw, Chi; Pm, Chen; Teng, Shu-Chun; Kj, Wu

doi:10.1038/sj.onc.1209929

Cited by 139 publications

(134 citation statements)

References 24 publications

(39 reference statements)

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“…16 In this study, we transfected SCC9 cells with either an empty vector (SCC9-N) or a vector encoding human Snail (SCC9-S). Six weeks later, the stable SCC9-N and SCC9-S cell lines were obtained.…”

Section: Overexpression Of Snail Correlates With Emtmentioning

confidence: 99%

mentioning

confidence: 99%

“…14 This process also occurs in the progression of carcinomas (including oral carcinoma cells), following the downregulation of E-cadherin expression or co-expression of NBS1. 13,[15][16][17] Snail also has been linked to cell survival or apoptosis, cell polarity, cancer cell invasion, recurrence, and the acquisition of cancer stem cell (CSC)-like characteristics. 14,18,19 Increasing evidence suggests that tumours develop and progress from a small subset of cells with the ability to selfrenew, which enter the cell cycle infrequently.…”

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Snail overexpression induces an epithelial to mesenchymal transition and cancer stem cell-like properties in SCC9 cells

Zhu

Yang

et al. 2012

Laboratory Investigation

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Local invasiveness and distant metastasis are critical factors that contribute to oral squamous cell carcinoma-related deaths. Increasing evidence has shown that the epithelial to mesenchymal transition (EMT) is involved in cancer progression and is associated with the 'stemness' of cancer cells. Snail is a transcriptional factor that can induce EMT and preserve stem-cell function, which may induce resistance to radio-and chemotherapies in the cells. In the present study, SCC9 cells were transfected with an empty vector or a vector encoding human Snail (SCC9-S). Overexpression of Snail induced SCC9 cells to undergo EMT, in which the cells presented a fibroblast-like appearance, downregulated the epithelial markers E-cadherin and b-catenin, upregulated the mesenchymal marker vimentin, and associated with highly invasive and metastatic properties. Furthermore, the induction of EMT promoted cancer stem cell (CSC)-like characteristics in the SCC9-S cells, such as low proliferation, self-renewal, and CSC-like markers expression. These results indicate that overexpression of Snail induces EMT and promotes CSC-like traits in the SCC9 cells. Further understanding the role of Snail in cancer progression may reveal new targets for the prevention or therapy of oral cancers. Oral squamous cell carcinoma (OSCC) is the most frequent type of cancer in the oral cavity and is associated with high morbidity and poor prognosis. 1,2 Despite progress in surgery, chemotherapy, and radiotherapy, the 5-year survival rate has remained at 50-55% over the past several decades. 3 Local or regional recurrences and distant metastases have a critical role in this process, and the mechanism underlying their occurrence remains poorly understood. 2,4 During metastatic progression, tumour cells lose cell-cell adhesion, detach from the primary site, invade the basement membrane, survive and circulate in the blood vessels, leave the bloodstream, and finally colonise in a new host environment to form micrometastases. 2,5-7 A growing body of research strongly suggests that the epithelial to mesenchymal transition (EMT), which occurs normally during embryonic development, tissue remodelling, and wound healing, is a critical early event in tumour invasion and metastasis. [8][9][10] It is characterised by downregulation of epithelial markers, such as E-cadherin, and upregulation of mesenchymal markers, such as vimentin. During the process of EMT, epithelial cells acquire mesenchymal cell properties and show reduced intercellular adhesion and increased invasion. 11 The transcriptional repressor Snail, which is a zinc finger protein, first described in Drosophila melanogaster, can bind to the E-boxes in the human E-cadherin promoter and suppress its transcription. 12,13 Snail has previously been implicated in triggering EMT during embryonic development, fibrosis, and tumour progression. 14 This process also occurs in the progression of carcinomas (including oral carcinoma cells), following the downregulation of E-cadherin expression or co-expression of NB...

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Section: Overexpression Of Snail Correlates With Emtmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Snail overexpression induces an epithelial to mesenchymal transition and cancer stem cell-like properties in SCC9 cells

Zhu

Yang

et al. 2012

Laboratory Investigation

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“…Epidermal growth factor receptor expression and activation have been demonstrated in some mesotheliomas, resulting in downstream activation of MAPK proliferation-associated signaling pathways (Pache et al, 1998;Yang et al, 2007). These studies suggest that epidermal growth factor receptor activation might play an early role in asbestos-induced mesothelial mitogenicity and carcinogenesis.…”

Section: Introductionmentioning

confidence: 98%

AXL regulates mesothelioma proliferation and invasiveness

et al. 2010

Oncogene

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Mesothelioma is an asbestos-associated and notoriously chemotherapy-resistant neoplasm. Activation of the receptor tyrosine kinases (RTKs), epidermal growth factor receptor and MET, has been described in subsets of mesothelioma, suggesting that TKs might represent therapeutic targets in this highly lethal disease. We employed proteomic screening by phosphotyrosine immunoaffinity purification and tandem mass spectrometry to characterize RTK activation in mesothelioma cell lines. These assays demonstrated expression and activation of the AXL protein, which is an RTK with known oncogenic properties in non-mesothelial cancer types. AXL was expressed and activated strongly in 8 of 9 mesothelioma cell lines and 6 of 12 mesothelioma biopsies, including each of 12 mesotheliomas with spindle-cell histology. Somatic AXL mutations were not found, but all mesotheliomas expressed an alternatively spliced AXL transcript with in-frame deletion of exon 10, and six of seven mesothelioma cell lines expressed the AXL ligand, growth arrest-specific 6 (GAS6). GAS6 expression appeared to be functionally relevant, as indicated by modulation of AXL tyrosine phosphorylation by knockdown of endogeneous GAS6, and by administration of exogenous GAS6. AXL silencing by lentivirus-mediated short hairpin RNA suppressed mesothelioma migration and cellular proliferation due to G1 arrest. The AXL inhibitor DP-3975 inhibited cell migration and proliferation in mesotheliomas with strong AXL activation. DP-3975 response in these tumors was characterized by inhibition of PI3-K/AKT/mTOR and RAF/MAPK signaling. AXL inhibition suppressed mesothelioma anchorage-independent growth, with reduction in colony numbers and size. These studies suggest that AXL inhibitors warrant clinical evaluation in mesothelioma.

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“…43 For real-time monitoring of cell migration, the xCELLigence system was used; 5 £ 10 4 cells/well were seeded onto the top chamber of a CIM plate, which features microelectronic sensors integrated on the underside of the microporous membrane of a Boydenlike chamber. The medium with SDF-1a (100 ng/ml) was added in the bottom chamber.…”

Section: Migration Assaysmentioning

confidence: 99%

LPS-induced CXCR4-dependent migratory properties and a mesenchymal-like phenotype of colorectal cancer cells

Liu

Jing

Yan

et al. 2016

Cell Adhesion & Migration

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Colorectal cancer (CRC) is the most commonly diagnosed cancer worldwide, and over 50% of patients will develop hepatic metastasis during the course of their disease. CXCR4 and its ligand, stromal cell-derived factor 1a (SDF-1a)/chemokine (C-X-C motif) ligand 12 (CXCL12) have been revealed as regulatory molecules involved in the spreading and progression of a variety of tumors. Here we have shown that lipopolysaccharides (LPS) promoted the migratory capacity of colon cancer cells in vivo and in vitro, which correlated with the activation of SDF-1a/CXCR4 axis and epithelial-mesenchymal transition (EMT) occurrence. Additionally, we found that LPS-induced CXCR4 expression and EMT through NF-kB signaling pathway activation. And inhibition of NF-kB pathway, which recovered the epithelial phenotype and attenuated CXCR4 expression, inhibited cell migratory capacity. Clinically, high levels of CXCR4 always correlated with metastasis and poor prognosis of CRC patients. In conclusion, LPS participate in the whole process of hepatic metastasis of CRC, not only causing liver damage resulting in the production of SDF-1a, but also enhancing the invasive potential of CRC cells by promoting CXCR4 expression and EMT occurrence, which would contribute to the enhancement of cell migration and invasion.

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Overexpression of NBS1 induces epithelial–mesenchymal transition and co-expression of NBS1 and Snail predicts metastasis of head and neck cancer

Cited by 139 publications

References 24 publications

Snail overexpression induces an epithelial to mesenchymal transition and cancer stem cell-like properties in SCC9 cells

Snail overexpression induces an epithelial to mesenchymal transition and cancer stem cell-like properties in SCC9 cells

AXL regulates mesothelioma proliferation and invasiveness

LPS-induced CXCR4-dependent migratory properties and a mesenchymal-like phenotype of colorectal cancer cells

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