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

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number983
JournalCell Death and Disease
Volume12
Issue number11
DOIs
Publication statusPublished - 2021 Nov

All Science Journal Classification (ASJC) codes

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

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