Snail-induced epithelial-mesenchymal transition promotes cancer stem cell-like phenotype in head and neck cancer cells

Masui, Tsuneo; Ota, Ichiro; Yook, Jong In; Mikami, Shinichi; Yane, Katsunari; Yamanaka, Toshiaki; Hosoi, Hiroshi

doi:10.3892/ijo.2013.2225

Cited by 62 publications

(50 citation statements)

References 48 publications

(42 reference statements)

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“…10,11 EMT plays an important role in the metastasis of HNSCC by facilitating primary tumor invasion through the basement membrane and migration through the tumor-associated stroma or extracellular matrix (ECM). [12][13][14] It has been reported that DDR2 is a critical regulator of EMT. 15 Though previous studies have investigated the function of DDR2 in some common tumors, there has not been functional characterization of the potential role of DDR2 in HNSCC.…”

Section: Introductionmentioning

confidence: 99%

Overexpression of DDR2 contributes to cell invasion and migration in head and neck squamous cell carcinoma

Lü

Zhang

et al. 2014

Cancer Biology & Therapy

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IntroductionHead and neck squamous cell carcinoma (HNSCC) represents approximately 6% of all cancers and about 500 000 cases are diagnosed every year.1 Over the past 20 years, diagnosis and management of HNSCC have improved through combined efforts in surgery, radiotherapy and chemotherapy, but the overall 5-y survival rate for patients is still only 40-50%. 2 The high rate of recurrence of HSNCC and its significant metastatic potential after conventional therapy appear to be major contributing factors for restricted survival of HNSCC patients.3 Therefore, understanding the molecular cancer pathways of underlying HNSCC metastasis would help to improve the therapy of the disease.Discoidin domain receptor 2 (DDR2) is a receptor tyrosine kinase (RTK) that can be activated by fibrillar collagens, 4-6 and implicated in several cancer cell behaviors, including VEGF expression, tumor angiogenesis, invasion, and metastasis. [7][8][9] Matrix metalloproteinases (MMPs) are an important subset of downstream target genes of DDR2 signaling. 10,11 EMT plays an important role in the metastasis of HNSCC by facilitating primary tumor invasion through the basement membrane and migration through the tumor-associated stroma or extracellular matrix (ECM).12-14 It has been reported that DDR2 is a critical regulator of EMT.15 Though previous studies have investigated the function of DDR2 in some common tumors, there has not been functional characterization of the potential role of DDR2 in HNSCC. Therefore, the aim of the current study was to investigate this issue. Results DDR2 is highly expressed in high-grade HNSCCIn order to explore the role of DDR2 in HNSCC, we first compared its expression levels in non-cancerous and cancer tissues. The results of real-time quantitative PCR (qPCR) showed that the mRNA expression level of DDR2 was much higher in all the tumor tissues than in their normal counterparts, and Keywords: DDR2, HNSCC, tumor metastasis, EMT, hypoxiaBackground: Discoidin domain receptor 2 (DDR2) is a unique receptor tyrosine kinase (RTK) that is activated by fibrillar collagens. although DDR2 contributes to the metastasis of some tumors, its role in head and neck squamous cell carcinoma (hNsCC) remains unknown. The aim of this study was to investigate the expression level, clinical and pathological significance, and biologic function of DDR2 in hNsCC.Methods: Real-time quantitative PCR, western blot, and immunohistochemical staining were employed to assess the expression levels of DDR2 in hNsCC specimens. adenovirus-mediated overexpression of DDR2 was used to evaluate its consequences on cell proliferation, invasion, migration, and the process of hypoxia-induced epithelial-mesenchymal transition (eMT). Then nude mouse xenograft and tail vein metastasis models were utilized to validate the in vitro results.Results: DDR2 was highly expressed in high grade hNsCC tissues and lowly expressed in low grade hNsCC tissues, but absent or rarely expressed in cancer-associated normal tissues. Both the frequency and expression intensit...

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Section: Introductionmentioning

confidence: 99%

Overexpression of DDR2 contributes to cell invasion and migration in head and neck squamous cell carcinoma

Lü

Zhang

et al. 2014

Cancer Biology & Therapy

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“…Our results revealed that the low-score subtype was significantly enriched by a hypoxia-induced gene set in HNSCC (21). The cancer stem cell-like phenotype was associated with chemo-resistance in head and neck cancer cells (22)(23)(24). We found that two stemness expression signatures were enriched in the low-score phenotype.…”

Section: Main Effect Of Variablesmentioning

confidence: 62%

Gene‑expression signature predicts survival benefit from postoperative chemoradiotherapy in head and neck squamous cell carcinoma

Jin

Chen

et al. 2018

Oncol Lett

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“…The changes in gene expression that contributed to the repression of the epithelial phenotype and activation of the mesenchymal phenotype involves the regulators Snail and Twist (33). Induction of Snail expression has been noted in all EMT processes that have been previously studied, and increased Snail levels have been correlated with more invasive tumor types (34)(35)(36). Snail regulated the expression level of epithelial or mesenchymal genes and it regulated the expression level of E-cadherin, which is downregulated during EMT (37).…”

Section: Discussionmentioning

confidence: 99%

Hispolon as an inhibitor of TGF-β-induced epithelial-mesenchymal transition in human epithelial cancer cells by co-regulation of TGF-β-Snail/Twist axis

et al. 2017

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Abstract. Hispolon (HPL), isolated from Phellinus linteus, has been used to treat various types of pathology, including inflammation, gastroenteric disorders, lymphatic diseases and numerous cancer subtypes. HPL has previously been reported to demonstrate a significant therapeutic efficacy against various types of cancer cells, including melanoma, leukemia, hepatocarcinoma, bladder and gastric cancer cells. However, its potential role in the epithelial-mesenchymal transition (EMT) has not been demonstrated. The present study investigated the effects of HPL on the EMT. Transforming growth factor β (TGF-β) induced enhanced cell migration and invasion, EMT-associated phenotypic changes. In the present study, HPL recovered the reduction of E-cadherin expression level in TGF-β treated cancer cells, which was regulated by the expression of Snail and Twist. HPL downregulated Snail and Twist, an effect that was enhanced by TGF-β. These findings provide novel evidence that HPL suppresses cancer cell migration and invasion by inhibiting EMT. Therefore, HPL may be a potent anticancer agent, inhibiting metastasis.

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Snail-induced epithelial-mesenchymal transition promotes cancer stem cell-like phenotype in head and neck cancer cells

Cited by 62 publications

References 48 publications

Overexpression of DDR2 contributes to cell invasion and migration in head and neck squamous cell carcinoma

Overexpression of DDR2 contributes to cell invasion and migration in head and neck squamous cell carcinoma

Gene‑expression signature predicts survival benefit from postoperative chemoradiotherapy in head and neck squamous cell carcinoma

Hispolon as an inhibitor of TGF-β-induced epithelial-mesenchymal transition in human epithelial cancer cells by co-regulation of TGF-β-Snail/Twist axis

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