Endothelial Cell-Secreted EGF Induces Epithelial to Mesenchymal Transition and Endows Head and Neck Cancer Cells with Stem-like Phenotype

Zhang, Zhaocheng; Dong, Zhihong; Lauxen, Isabel S.; Filho, Manoel Sant’Anna; Nör, Jacques E.

doi:10.1158/0008-5472.can-13-2032

Cited by 110 publications

(123 citation statements)

References 43 publications

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“…The value of CD44 as a marker of OSCC progression and prognosis is also controversial. Certain studies in HNSCC have reported aldehyde dehydrogenase (ALDH) + cells with typical CSC behavior, in particular the tumorigenic ability (55)(56)(57)(58). The specificity of CD44 as a marker of CSCs in HNSCC is reported to be increased in combination with ALDH (55,56).…”

Section: Concept and Identification Of Cscsmentioning

confidence: 99%

Expression of SOX2 in oral squamous cell carcinoma and the association with lymph node metastasis

Ren

Zhang

2016

Oncology Letters

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Abstract. Oral squamous cell carcinomas (OSCCs) are a growing problem in the world. The various existing treatments have not markedly improved the survival rate of patients with OSCC during the past three decades. Novel treatment strategies are required. Sex determining region Y-box 2 (SOX2) is a transcription factor that is involved in the maintenance of embryonic stem cell pluripotency and in multiple developmental processes. SOX2 expression was indicated to act as a prognostic factor in various types of tumors, including breast, colorectal, gastric and lung cancer and glioblastoma, and as a link between malignancy and stemness. Cancer stem cells (CSCs) may be responsible for the genesis, growth and metastatic spread of tumors. The poor survival outcomes for OSCC patients may be attributable to a poor selection of target cells for treatment, as current oral cancer therapies are generally aimed at the global mass of tumor. Therefore, the consideration that novel approaches to oral cancer may be targeted using SOX2 and CSCs appears reasonable. In order to better understand the oncogenic roles and the corresponding signal transduction pathways of the SOX2 protein, the present study emphasizes the role of SOX2 in OSCC, including the proteins associated with OSCC, and reviews the literature regarding the role of SOX2 in lymph node metastasis. The aim of the present study is to provide a reference for future studies that engage in research on the aforementioned subject.

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Section: Concept and Identification Of Cscsmentioning

confidence: 99%

Expression of SOX2 in oral squamous cell carcinoma and the association with lymph node metastasis

Ren

Zhang

2016

Oncology Letters

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“…There are also changes in cellular proteins, such as integrins and a-smooth muscle actin, as well as ECM proteins, such as collagen, laminin, and fibronectin. 149,[213][214][215][216][220][221][222][223] The HNSCC cells that undergo EMT have been shown to be more invasive. * The loss of E-cadherin associated with EMT is an indicator of poor prognosis in HNSCC.…”

Section: 213-219mentioning

confidence: 99%

“…225,226 Cancer stem cells exhibit the properties of self-renewal, potential to behave as tumor progenitor cells, and the ability to differentiate. 223,[225][226][227] Cancer stem cells are slow-dividing and therefore often more resistant to chemotherapy. [225][226][227] Cancer stem cells are found in invasive fronts, and in many tumors are near the blood vessels.…”

Section: 213-219mentioning

confidence: 99%

“…[225][226][227] Cancer stem cells are found in invasive fronts, and in many tumors are near the blood vessels. 217,223,[225][226][227] Epithelial to mesenchymal transition can generate cells within tumors that have stemlike properties. 216,219,223,228 In head and neck cancer, Twist, a regulator of EMT, was found to induce expression of Bmi-1, a regulator of stemness.…”

Section: 213-219mentioning

confidence: 99%

“…217,223,[225][226][227] Epithelial to mesenchymal transition can generate cells within tumors that have stemlike properties. 216,219,223,228 In head and neck cancer, Twist, a regulator of EMT, was found to induce expression of Bmi-1, a regulator of stemness. 219,228 Twist and Bmi-1 can act together to repress expression of E-cadherin and p16INK4a.…”

Section: 213-219mentioning

confidence: 99%

See 2 more Smart Citations

Mechanisms of Invasion in Head and Neck Cancer

Jimenez¹,

Jayakar²,

Ow³

et al. 2015

Archives of Pathology &Amp; Laboratory Medicine

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Context.-The highly invasive properties demonstrated by head and neck squamous cell carcinoma (HNSCC) are often associated with locoregional recurrence and lymph node metastasis in patients and is a key factor leading to an expected 5-year survival rate of approximately 50% for patients with advanced disease. It is important to understand the features and mediators of HNSCC invasion so that new treatment approaches can be developed.Objectives.-To provide an overview of the characteristics, mediators, and mechanisms of HNSCC invasion.Data Sources.-A literature review of peer-reviewed articles in PubMed on HNSCC invasion.Conclusions.-Histologic features of HNSCC tumors can help predict prognosis and influence clinical treatment decisions. Cell surface receptors, signaling pathways, proteases, invadopodia function, epithelial-mesenchymal transition, microRNAs, and tumor microenvironment are all involved in the regulation of the invasive behavior of HNSCC cells. Identifying effective HNSCC invasion inhibitors has the potential to improve outcomes for patients by reducing the rate of spread and increasing responsiveness to chemoradiation.

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Src promotes EGF‐induced epithelial‐to‐mesenchymal transition and migration in gastric cancer cells by upregulating ZEB1 and ZEB2 through AKT

Zhao

Song

et al. 2017

Cell Biology International

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Epithelial-to-mesenchymal transition (EMT) plays important roles in the migration, invasion, and metastasis of cancer cells. However, the role of Src in epidermal growth factor (EGF)-induced EMT and migration in gastric cancer cells remains to be clarified. In the current study, the effect of Src on EGF-stimulated EMT and migration was explored in gastric cancer cells. EGF induced EMT in gastric cancer cells and increased their migratory ability, which was accompanied by the phosphorylation of Src. PP2, the Src inhibitor, markedly suppressed EGF-mediated EMT and migration in gastric cancer cells. Additionally, EGF-stimulated upregulation of zinc finger E-box binding homeobox 1 (ZEB1) and zinc finger E-box binding homeobox 2 (ZEB2) was significantly repressed by PP2. Further analysis showed that EGF-stimulated phosphorylation of protein kinase B (AKT) was almost completely abolished by PP2, whereas that of extracellular signal-regulated kinase (ERK), signal transducer and activator of transcription 3 (STAT3) was only mildly suppressed. Moreover, LY294002, the AKT inhibitor, significantly inhibited EGF-induced upregulation of ZEB1 and ZEB2 as well as EMT and migration stimulated by EGF in gastric cancer cells. However, neither ERK inhibitor nor STAT3 inhibitor repressed EGF-induced EMT-related changes. Taken together, these results suggest that Src promotes EGF-stimulated EMT and migration by upregulation of ZEB1 and ZEB2 through AKT signaling pathway in gastric cancer cells.

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Endothelial Cell-Secreted EGF Induces Epithelial to Mesenchymal Transition and Endows Head and Neck Cancer Cells with Stem-like Phenotype

Cited by 110 publications

References 43 publications

Expression of SOX2 in oral squamous cell carcinoma and the association with lymph node metastasis

Expression of SOX2 in oral squamous cell carcinoma and the association with lymph node metastasis

Mechanisms of Invasion in Head and Neck Cancer

Src promotes EGF‐induced epithelial‐to‐mesenchymal transition and migration in gastric cancer cells by upregulating ZEB1 and ZEB2 through AKT

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