CPAP enhances and maintains chronic inflammation in hepatocytes to promote hepatocarcinogenesis

Ruo Yu Chen, Chia Jui Yen, Yih Jyh Lin, Ju Ming Wang, Ting Fen Tasi, Yu Chuan Huang, Yao Wen Liu, Hung Wen Tsai, Ming Hao Lee, Liang Yi Hung

研究成果: Article同行評審

2 引文 斯高帕斯(Scopus)

摘要

Chronic and persistent inflammation is a well-known carcinogenesis promoter. Hepatocellular carcinoma (HCC) is one of the most common inflammation-associated cancers; most HCCs arise in the setting of chronic inflammation and hepatic injury. Both NF-κB and STAT3 are important regulators of inflammation. Centrosomal P4.1-associated protein (CPAP), a centrosomal protein that participates primarily in centrosome functions, is overexpressed in HCC and can increase TNF-α-mediated NF-κB activation and IL-6-induced STAT3 activation. A transgenic (Tg) mouse model with hepatocyte-specific CPAP expression was established to investigate the physiological role of CPAP in hepatocarcinogenesis. Obvious inflammatory cell accumulation and fatty change were observed in the livers of CPAP Tg mice. The alanine aminotransferase (ALT) level and the expression levels of inflammatory genes, such as IL-6, IL-1β and TNF-α, were higher in CPAP Tg mice than in wild type (WT) mice. High-dose/short-term treatment with diethylnitrosamine (DEN) increased the ALT level, proinflammatory gene expression levels, and STAT3 and NF-κB activation in CPAP Tg mice; low-dose/long-term DEN treatment induced more severe liver tumor formation in CPAP Tg mice than in WT mice. CPAP can increase the expression of chemokine (C-C motif) ligand 16 (CCL-16), an important chemotactic cytokine, in human hepatocytes. CCL-16 expression is positively correlated with CPAP and TNF-α mRNA expression in the peritumoral part of HCC. In summary, these results suggest that CPAP may promote hepatocarcinogenesis through enhancing the inflammation pathway via increasing the expression of CCL-16.

原文English
文章編號983
期刊Cell Death and Disease
12
發行號11
DOIs
出版狀態Published - 2021 11月

All Science Journal Classification (ASJC) codes

  • 免疫學
  • 細胞與分子神經科學
  • 細胞生物學
  • 癌症研究

指紋

深入研究「CPAP enhances and maintains chronic inflammation in hepatocytes to promote hepatocarcinogenesis」主題。共同形成了獨特的指紋。

引用此