Reduced expression levels of the death-associated protein kinase and E-cadherin are correlated with the development of esophageal squamous cell carcinoma

AbstractNatural antisense lncRNAs can interfere with their corresponding sense transcript to elicit concordant or discordant regulation. LncRNA ZNF667-AS1 and its sense gene ZNF667 were found to be downregulated in esophageal squamous cell carcinoma (ESCC) tissues by RNA sequencing; however, the exact roles of both genes in ESCC occurrence and development have not been clarified. This study was to investigate the expression patterns, epigenetic inactivation mechanisms, function, and prognostic significance of ZNF667-AS1 and ZNF667 in ESCC tumorigenesis. Frequent downregulation of ZNF667-AS1 and ZNF667 was detected in esophageal cancer cells and ESCC tissues. The expression levels of ZNF667-AS1 and ZNF667 were significantly reversed by treatment with 5-Aza-dC and TSA in esophageal cancer cell lines. The CpG sites hypermethylation within proximal promoter influenced the binding ability of transcription factor E2F1 to the binding sites and then affected the transcription and expression of ZNF667-AS1 and ZNF667. Overexpression of ZNF667-AS1 and ZNF667 suppressed the viability, migration, and invasion of esophageal cancer cells in vitro. Overexpression of ZNF667-AS1 increased mRNA and protein expression level of ZNF667. ZNF667-AS1 interacts with and recruits TET1 to its target gene ZNF667 and E-cadherin to hydrolyze 5′-mc to 5′-hmc and further activates their expression, meanwhile, ZNF667-AS1 also interacts with UTX to decrease histone H3K27 tri-methylation to activate ZNF667 and E-cadherin expression. Furthermore, ZNF667-AS1 or ZNF667 expression and promoter methylation status were correlated with ESCC patients’ survival. Thus, these findings suggest that ZNF667-AS1 and ZNF667 may act as tumor suppressors and may serve as potential targets for antitumor therapy.

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α-catenin is a significant prognostic factor than E-cadherin in esophageal squamous cell carcinoma

Journal of Surgical Oncology ◽

10.1002/jso.20610 ◽

2007 ◽

Vol 95 (2) ◽

pp. 148-155 ◽

Cited By ~ 17

Author(s):

Tetsuro Setoyama ◽

Shoji Natsugoe ◽

Hiroshi Okumura ◽

Masataka Matsumoto ◽

Yasuto Uchikado ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Prognostic Factor ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Significant Prognostic Factor ◽

E Cadherin

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Dysregulation of Claudin-7 Leads to Loss of E-Cadherin Expression and the Increased Invasion of Esophageal Squamous Cell Carcinoma Cells

American Journal Of Pathology ◽

10.2353/ajpath.2007.060343 ◽

2007 ◽

Vol 170 (2) ◽

pp. 709-721 ◽

Cited By ~ 80

Author(s):

Mercedes Lioni ◽

Patricia Brafford ◽

Claudia Andl ◽

Anil Rustgi ◽

Wafik El-Deiry ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Carcinoma Cells ◽

E Cadherin

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E-Cadherin Expression in Patients With Esophageal Squamous Cell Carcinoma

American Journal of Clinical Pathology ◽

10.1309/wjl90jpem17rbuht ◽

2004 ◽

Vol 122 (1) ◽

pp. 78-84 ◽

Cited By ~ 39

Author(s):

Shinsuke Takeno ◽

Tsuyoshi Noguchi ◽

Shoichi Fumoto ◽

Yasuhiko Kimura ◽

Tomotaka Shibata ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

E Cadherin

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TOPK Promotes Metastasis of Esophageal Squamous Cell Carcinoma by Activating Src/GSK3β/STAT3 Signal Pathway though γ-catenin

10.21203/rs.2.13096/v1 ◽

2019 ◽

Author(s):

Yanan Jiang ◽

Jing Zhang ◽

Jimin Zhao ◽

Zhenzhen Li ◽

Hanyong Chen ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Protein Kinase ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Lung Metastasis ◽

Squamous Cell ◽

Tissue Array ◽

Erk Pathway ◽

Mice Model

Abstract Background Esophageal squamous cell carcinoma (ESCC) is a deadly disease with the poor prognosis in the world. The distal metastasis is the most death reason of ESCC. It is needed to have a comprehensive understanding of the molecular mechanism of metastasis to increase the free survive rate. T-LAK cell-originated protein kinase (TOPK) which is a MAPKK-like kinase takes an vital role in many physical and pathophysiological progress. However, the function of TOPK in ESCC metastasis was unclear. Methods Tissue array was used to evaluate the relationship between TOPK and ESCC patient with lymph node metastasis. Wound healing assay, transwell assay and lung metastasis mice model were assessed for the role of TOPK in the migration of ESCC cells in vitro and in vivo respectively. Protein kinase array, MS and molecular modeling were carried out to find the relational pathways and target protein of TOPK. Even, immune-fluorescence and western blot were performed to evaluate the mechanism of TOPK. Results We found that the high level of TOPK was correlated with the aggressive phenotype in ESCC tissues. Knocking down TOPK inhibited the invasion and migration of ESCC cells. We also verified that TOPK inhibitor HI-TOPK-032 inhibited the lung metastasis in ESCC cell exnograft model. Even more, molecular investigation indicated that TOPK promoted the invasion of ESCC cells by activing Src/GSK3β/STAT3, ERK pathway by binding with γ-catenin. Conclusion These findings reveal that TOPK was sincerely related with ESCC cell metastasis and TOPK promoted the invasion of ESCC cells by activing Src/GSK3β/STAT3, ERK pathway. This means that TOPK may be a potential molecular target for ESCC in clinic.

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CD73 Promotes Tumor Progression in Patients with Esophageal Squamous Cell Carcinoma

Cancers ◽

10.3390/cancers13163982 ◽

2021 ◽

Vol 13 (16) ◽

pp. 3982

Author(s):

Yen-Hao Chen ◽

Hung-I Lu ◽

Chien-Ming Lo ◽

Shau-Hsuan Li

Keyword(s):

Squamous Cell Carcinoma ◽

Prognostic Factor ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Disease Free Survival ◽

Independent Prognostic Factor ◽

Expression Levels ◽

Invasion And Migration ◽

Patient Responses

Cluster of differentiation (CD)-73 plays pivotal roles in the regulation of immune reactions via the production of extracellular adenosine, and the overexpression of CD73 is associated with worse outcomes in several types of cancers. Here, we identified 167 esophageal squamous cell carcinoma (ESCC) patients who underwent esophagectomy, including 64 and 103 patients with high and low expression levels of CD73, respectively. Univariate and multivariate analyses showed high expression of CD73 was an independent prognostic factor for worse disease-free survival and overall survival. In addition, we selected another cohort consisting of 38 ESCC patients receiving nivolumab or pembrolizumab and found that treatment response and survival benefit to immunotherapy were strongly correlated with the expression levels of CD73/programmed death ligand 1. Moreover, the transwell assay revealed knockdown of CD73 in two ESCC cell lines, TE1 and KYSE30, exhibited significantly reduced abilities of cell invasion and migration. CD73 silencing also showed that the protein expression levels of CD73, vimentin, and snail were downregulated, while those of E-cadherin were upregulated in Western blotting. The findings of our study indicate CD73 may be an independent prognostic factor for ESCC patients who underwent esophagectomy. Furthermore, it may be associated with the patient responses to immunotherapy.

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