Tonicity-responsive enhancer binding protein promotes hepatocellular carcinogenesis, recurrence, and metastasis

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Title
Tonicity-responsive enhancer binding protein promotes hepatocellular carcinogenesis, recurrence, and metastasis
Author(s)
Jun Ho Lee; Jae Hee Suh; Soo Youn Choi; Hyun Je Kang; Hwan Hee Lee; Byeong Jin Ye; Gap Ryol Lee; Seok Won Jung; Chang Jae Kim; Whaseon Lee-Kwon; Jiyoung Park; Kyungjae Myung; Neung Hwa Park; Hyug Moo Kwon
Publication Date
2018-02
Journal
GUT, v.29, no.2, pp.492 - 504
Publisher
B M J PUBLISHING GROUP
Abstract
Objectives Hepatocellular carcinoma (HCC) is a common cancer with high rate of recurrence and mortality. Diverse aetiological agents and wide heterogeneity in individual tumours impede effective and personalised treatment. Tonicity-responsive enhancer-binding protein (TonEBP) is a transcriptional cofactor for the expression of proinflammatory genes. Although inflammation is intimately associated with the pathogenesis of HCC, the role of TonEBP is unknown. We aimed to identify function of TonEBP in HCC. Design T umours with surrounding hepatic tissues were obtained from 296 patients with HCC who received completion resection. TonEBP expression was analysed by quantitative reverse transcription–quantitative realtime PCR (RT -PCR) and immunohfistochemical analyses of tissue microarrays. Mice with TonEBP haplo deficiency, and hepatocyte-specific and myeloid-specific TonEBP deletion were used along with HCC and hepatocyte cell lines. Results T onEBP expression is higher in tumours than in adjacent non-tumour tissues in 92.6% of patients with HCC regardless of aetiology associated. The TonEBP expression in tumours and adjacent non-tumour tissues predicts recurrence, metastasis and death in multivariate analyses. TonEBP drives the expression of cyclo-oxygenase-2 (COX-2) by stimulating the promoter. In mouse models of HCC, three common sites of TonEBP action in response to diverse aetiological agents leading to tumourigenesis and tumour growth were found: cell injury and inflammation, induction by oxidative stress and stimulation of the COX-2 promoter. Conclusions T onEBP is a key component of the common pathway in tumourigenesis and tumour progression of HCC in response to diverse aetiological insults. TonEBP is involved in multiple steps along the pathway, rendering it an attractive therapeutic target as well as a prognostic biomarker. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
URI
https://pr.ibs.re.kr/handle/8788114/4999
ISSN
0017-5749
Appears in Collections:
Center for Genomic Integrity(유전체 항상성 연구단) > Journal Papers (저널논문)
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