CCL14 serves as a novel prognostic factor and tumor suppressor of HCC by modulating cell cycle and promoting apoptosis

• Published in: Cell death & disease Vol. 10; no. 11; pp. 796 - 10
• Main Authors: Zhu, Mengxuan, Xu, Weiyue, Wei, Chuanyuan, Huang, Jing, Xu, Jietian, Zhang, Yuye, Zhao, Yan, Chen, Jie, Dong, Shuangshuang, Liu, Binbin, Liang, Chunmin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22.10.2019; Springer Nature B.V
• Subjects: 13; 13/105; 13/2; 13/31; 631/67/2195; 692/308/53/2421; Animal models; Animals; Antibodies; Apoptosis; Apoptosis - physiology; Biochemistry; Biomarkers, Tumor - biosynthesis; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Biomedical and Life Sciences; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; CC chemokines; Cell Biology; Cell Culture; Cell cycle; Cell Cycle - physiology; Cell Line, Tumor; Cell proliferation; Chemokines, CC - biosynthesis; Chemokines, CC - genetics; Chemokines, CC - metabolism; Cirrhosis; Down-Regulation; Female; Hep G2 Cells; Hepatocellular carcinoma; Heterografts; Humans; Immunohistochemistry; Immunology; Life Sciences; Liver cancer; Liver cirrhosis; Liver Neoplasms - genetics; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Male; Mice; Mice, Nude; Prognosis; Tumor suppressor genes; Wnt protein; Xenografts; β-Catenin
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-019-1966-6

CCL14 is a member of CC chemokines and its role in hepatocellular carcinoma (HCC) is still unknown. In this study, CCL14 expression were analyzed by tissue microarray (TMA) including 171 paired tumor and peritumor tissues of patients from Zhongshan Hospital of Fudan University. We found for the first time that CCL14 was downregulated in HCC tumor tissues compared with peritumor tissues ( P  = 0.01). Meanwhile, CCL14 low expression in HCC tumor tissues is associated with a poor prognosis ( P  = 0.035). CCL14 also displayed its predictive value in high differentiation ( P  = 0.026), liver cirrhosis ( P  = 0.003), and no tumor capsule ( P  = 0.024) subgroups. The underlying mechanisms were further investigated in HCC cell lines by CCL14 overexpression and knock-down in vitro. We found overexpression of CCL14 suppressed proliferation and promoted apoptosis of HCC cells. Finally, the effect was confirmed by animal xenograft tumor models in vivo. The results shown overexpression of CCL14 lead to inhibiting the growth of tumor in nude mice. Interestingly, our data also implied that CCL14 played these effects by inhibiting the activation of Wnt/β-catenin pathway. These findings suggest CCL14 is a novel prognostic factor of HCC and serve as a tumor suppressor.