Abstract 1109: CPAP promotes HCC angiogenesis and metastasis via interacting with and enhancing STAT3 signaling

Abstract

Centrosomal P4.1-associated protein (CPAP) is a centrosomal protein and can as a transcriptional coactivator of STAT5 and NF-κB in cancer. Our previous studies indicated that CPAP is overexpressed in tumor tissue and can increase TNFα-mediated NF-κB activation in HCC. Here, we demonstrated that overexpressed CPAP increases tumor growth, angiogenesis, as well as metastasis ex vivo and in vivo . We found that CPAP increases these malignant abilities of tumor cells are through IL-6/STAT3 signaling. We demonstrated that CPAP directly interacts with C-terminal domain of STAT3 to increase STAT3 activity. Overexpression of CPAP enhances IL-6/STAT3/IL-8-mediated angiogenesis and other metastatic genes expression such as CD44 and MCAM. These results indicated that CPAP leads to HCC malignancy and metastasis by increasing STAT3 activity through directly interaction. Clinically, CPAP positively correlates with IL-8 in HCC with vascular invasion; and also positively correlates with CD44 and MCAM in HCC tissues. In summary, our findings shed light on the importance of CPAP to act as a potential therapeutic target for inhibiting the IL-6/STAT3-mediated angiogenesis pathway and treating metastatic HCC. Citation Format: Ruo Yu Chen, Liang-Yi Hung. CPAP promotes HCC angiogenesis and metastasis via interacting with and enhancing STAT3 signaling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1109.