EZH2 is associated with poor prognosis in head-and-neck squamous cell carcinoma via regulating the epithelial-to-mesenchymal transition and chemosensitivity

Chang, Jae Won; Gwak, Seo Young; Shim, Geunae; Liu, Lihua; Lim, Young Chang; Kim, Jin Man; Jung, Min Gyu; Koo, Bon Seok

doi:10.1016/j.oraloncology.2015.11.002

Cited by 57 publications

(52 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…After 48 h incubation for SNU1041 cells and 72 h for SCC15 cells, viability was measured using the Cell Proliferation Reagent WST-1 (Roche Diagnostics Corporation, Indianapolis, IN, USA) as described previously717. Results are presented as percentages relative to control cells.…”

Section: Methodsmentioning

confidence: 99%

Carboxyl-Terminal Modulator Protein Positively Acts as an Oncogenic Driver in Head and Neck Squamous Cell Carcinoma via Regulating Akt phosphorylation

Chang

Jung

Kim

et al. 2016

Sci Rep

Self Cite

View full text Add to dashboard Cite

The exact regulatory mechanisms of carboxyl-terminal modulator protein (CTMP) and its downstream pathways in cancer have been controversial and are not completely understood. Here, we report a new mechanism of regulation of Akt serine/threonine kinase, one of the most important dysregulated signals in head and neck squamous cell carcinoma (HNSCC) by the CTMP pathway and its clinical implications. We find that HNSCC tumor tissues and cell lines had relatively high levels of CTMP expression. Clinical data indicate that CTMP expression was significantly associated with positive lymph node metastasis (OR = 3.8, P = 0.033) and correlated with poor prognosis in patients with HNSCC. CTMP was also positively correlated with Akt/GSK-3β phosphorylation, Snail up-regulation and E-cadherin down-regulation, which lead to increased proliferation and epithelial-to-mesenchymal transition, suggesting that CTMP expression results in enhanced tumorigenic and metastatic properties of HNSCC cells. Moreover, CTMP suppression restores sensitivity to cisplatin chemotherapy. Intriguingly, all the molecular responses to CTMP regulation are identical regardless of p53 status in HNSCC cells. We conclude that CTMP promotes Akt phosphorylation and functions as an oncogenic driver and prognostic marker in HNSCC irrespective of p53.

show abstract

Section: Methodsmentioning

confidence: 99%

Carboxyl-Terminal Modulator Protein Positively Acts as an Oncogenic Driver in Head and Neck Squamous Cell Carcinoma via Regulating Akt phosphorylation

Chang

Jung

Kim

et al. 2016

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…EZH2 expression in colorectal cancer was reported to positively associate with TNM stage and lymph node metastasis [21] while another study evaluating the role of EZH2 expression in gastrointestinal malignancies, found that its overexpression is correlated with poor prognosis in esophageal but not colorectal and gastric cancer [22]. Moreover, EZH2 has been strongly associated with advanced stage and poor prognosis in squamous cell malignancies including cervical cancer [23], esophageal squamous cell carcinoma [24] and head and neck cancer [25]. Particularly, EZH2 promotes the epithelial to mesenchymal transformation (EMT) in head and neck carcinomas and decreases the sensitivity to cisplatin-based chemotherapy [25].…”

Section: Evidence Correlating Ezh2 Function With Cancermentioning

confidence: 99%

“…Moreover, EZH2 has been strongly associated with advanced stage and poor prognosis in squamous cell malignancies including cervical cancer [23], esophageal squamous cell carcinoma [24] and head and neck cancer [25]. Particularly, EZH2 promotes the epithelial to mesenchymal transformation (EMT) in head and neck carcinomas and decreases the sensitivity to cisplatin-based chemotherapy [25]. …”

Section: Evidence Correlating Ezh2 Function With Cancermentioning

confidence: 99%

Epigenetic regulation of cancer biology and anti-tumor immunity by EZH2

et al. 2016

View full text Add to dashboard Cite

Polycomb group proteins regulate chromatin structure and have an important regulatory role on gene expression in various cell types. Two polycomb group complexes (Polycomb repressive complex 1 (PRC1) and 2 (PRC2)) have been identified in mammalian cells. Both PRC1 and PRC2 compact chromatin, and also catalyze histone modifications. PRC1 mediates monoubiquitination of histone H2A, whereas PRC2 catalyzes methylation of histone H3 on lysine 27. These alterations of histones can lead to altered gene expression patterns by regulating chromatin structure. Numerous studies have highlighted the role of the PRC2 catalytic component enhancer of zeste homolog 2 (EZH2) in neoplastic development and progression, and EZH2 mutations have been identified in various malignancies. Through modulating the expression of critical genes, EZH2 is actively involved in fundamental cellular processes such as cell cycle progression, cell proliferation, differentiation and apoptosis. In addition to cancer cells, EZH2 also has a decisive role in the differentiation and function of T effector and T regulatory cells. In this review we summarize the recent progress regarding the role of EZH2 in human malignancies, highlight the molecular mechanisms by which EZH2 aberrations promote the pathogenesis of cancer, and discuss the anti-tumor effects of EZH2 targeting via activating direct anti-cancer mechanisms and anti-tumor immunity.

show abstract

“…The enhancer of zeste homolog 2 (EZH2), known as a member of the polycomb group (PcG) proteins, is a histone methyltransferase closely correlated with tumour aggressiveness in a variety of human malignancies, including oral, nasopharyngeal, gastric, hepatocellular, colon, renal, prostate and lung cancers . In a study of head and neck squamous cell carcinoma, EZH2 was associated with tumour aggressiveness via regulating EMT, and EZH2 silencing increased E‐cadherin while decreasing N‐cadherin and vimentin . Another study of laryngeal squamous cell carcinoma revealed that EZH2 could promote invasion and metastasis via EMT through catalysing trimethylation of lysine 27 in histone 3 (H3K27me3) and consequently inducing transcriptional repression of E‐cadherin .…”

Section: Introductionmentioning

confidence: 99%

EZH2 promotes invasion and tumour glycolysis by regulating STAT3 and FoxO1 signalling in human OSCC cells

Zheng

Cao

Luo

et al. 2019

J Cellular Molecular Medi

View full text Add to dashboard Cite

The enhancer of zeste homolog 2 (EZH2), known as a member of the polycomb group (PcG) proteins, is an oncogene overexpressed in a variety of human cancers. Here, we found that EZH2 correlated with poor survival of oral squamous cell carcinoma (OSCC) patients using immunohistochemistry staining. EZH2 overexpression led to a significant induction in tumour glycolysis, Epithelial‐mesenchymal transition (EMT), migration and invasion of OSCC cells. Conversely, silencing of EZH2 inhibited tumour glycolysis, EMT, migration and invasion in OSCC cells. Ectopic overexpression of EZH2 increased phosphorylation of STAT3 at pY705 and decreased FoxO1 expression, and FoxO1 expression was enhanced when inhibiting STAT3. In addition, EZH2 overexpression led to a significant decrease in FoxO1 mRNA levels in nude mice xenograft. These results indicated that regulation of EZH2 might have the potential to be targeted for OSCC treatment.

show abstract

EZH2 is associated with poor prognosis in head-and-neck squamous cell carcinoma via regulating the epithelial-to-mesenchymal transition and chemosensitivity

Cited by 57 publications

References 32 publications

Carboxyl-Terminal Modulator Protein Positively Acts as an Oncogenic Driver in Head and Neck Squamous Cell Carcinoma via Regulating Akt phosphorylation

Carboxyl-Terminal Modulator Protein Positively Acts as an Oncogenic Driver in Head and Neck Squamous Cell Carcinoma via Regulating Akt phosphorylation

Epigenetic regulation of cancer biology and anti-tumor immunity by EZH2

EZH2 promotes invasion and tumour glycolysis by regulating STAT3 and FoxO1 signalling in human OSCC cells

Contact Info

Product

Resources

About