Abstract 4415: CPAP contributes to HCC malignancy through regulating inflammatory pathways

Abstract

Abstract Hepatocellular carcinoma (HCC) is one of the most common malignancies, and the third most prevalent cause of cancer-related death worldwide. Its curative treatments are limited to liver resection and liver transplantation. In addition, HCC is characterized by hypervascular tumor which is described as a formation of many blood vessels during tumor growth. It has been shown that the transcription factors NF-κB and STAT3, both of which play an important role in the inflammatory pathway, are activated in HCC. Centrosomal P4.1-associated protein (CPAP) plays a vital role in centrosomal function and is identified as a transcriptional co-activator of NF-κB or STAT5. Our studies indicated that CPAP is overexpressed in HCC and involved in regulating the TNF-α-NF-κB and IL-6/STAT3 pathways. By reporter assay, Q-PCR, immunoblotting and ELISA analysis, we found that the activity of NF-κB or STAT3 is increased in HCC cells with CPAP overexpression upon TNF-α or IL-6 stimulation. Overexpressed GFP-CPAP significantly enhances NF-κB or STAT3-driven transcriptional activation and increases the expression of NF-κB or STAT3-targeted genes in response to TNF-α or IL-6 treatment. Furthermore, by immuoprecipitation and in situ PLA, CPAP could form a complex with NF-κB or STAT3. Expression of CPAP and NF-κB or STAT3 had a positive correlation in clinical HCC tissues. Interestingly, overexpression of GFP-CPAP augmented the expressions of pro-inflammatory cytokines and promoted tumor growth and metastasis in the orthotopic and splenic mouse models. The expression of CPAP was positively correlated with plasma proinflammatory cytokines expression in HCC patients. Our results suggest that CPAP participates in activating the TNF-α-NF-κB and IL-6/STAT3 pathways, which contributes to HCC malignancy. Citation Format: Liang-Yi Hung. CPAP contributes to HCC malignancy through regulating inflammatory pathways. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4415.