Xue Ruyi, Tang Wenqing, Dong Pingping, Weng Shuqiang, Ma Lijie, Chen She, Liu Taotao, Shen Xizhong, Huang Xiaowu, Zhang Si, Dong Ling
Department of Gastroenterology and Hepatology, Shanghai Institute of Liver Diseases, Zhongshan Hospital of Fudan University, Shanghai 200032, China.
Department of Hepatic Surgery of Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Int J Mol Sci. 2016 Sep 27;17(10):1626. doi: 10.3390/ijms17101626.
The calcium-dependent activator protein for secretion 1 (CAPS1) regulates exocytosis of dense-core vesicles (DCVs) in neurons and neuroendocrine cells. The role of CAPS1 in cancer biology remains unknown. The purpose of this study was to investigate the role of CAPS1 in hepatocellular carcinoma (HCC). We determined the levels of CAPS1 in eight hepatoma cell lines and 141 HCC specimens. We evaluated the prognostic value of CAPS1 expression and its association with clinical parameters. We investigated the biological consequences of CAPS1 overexpression in two hepatoma cell lines in vitro and in vivo. The results showed that loss of CAPS1 expression in HCC tissues was markedly correlated with aggressive tumor phenotypes, such as high-grade tumor node metastasis (TNM) stage ( = 0.003) and absence of tumor encapsulation ( = 0.016), and was associated with poor overall survival ( = 0.008) and high recurrence ( = 0.015). CAPS1 overexpression inhibited cell proliferation and migration by changing the exocytosis-associated tumor microenvironment in hepatoma cells in vitro. The in vivo study showed that CAPS1 overexpression inhibited xenograft tumor growth. Together, these results identified a previously unrecognized tumor suppressor role for CAPS1 in HCC development.
分泌型钙依赖性激活蛋白1（CAPS1）调节神经元和神经内分泌细胞中致密核心囊泡（DCV）的胞吐作用。CAPS1在癌症生物学中的作用尚不清楚。本研究的目的是探讨CAPS1在肝细胞癌（HCC）中的作用。我们测定了8种肝癌细胞系和141例HCC标本中CAPS1的水平。我们评估了CAPS1表达的预后价值及其与临床参数的关联。我们研究了CAPS1在两种肝癌细胞系中体外和体内过表达的生物学后果。结果显示，HCC组织中CAPS1表达缺失与侵袭性肿瘤表型显著相关，如高级别肿瘤淋巴结转移（TNM）分期（P = 0.003）和无肿瘤包膜（P = 0.016），并与总体生存率低（P = 0.008）和高复发率（P = 0.015）相关。体外实验中，CAPS1过表达通过改变肝癌细胞中与胞吐作用相关的肿瘤微环境来抑制细胞增殖和迁移。体内研究表明，CAPS1过表达抑制异种移植肿瘤生长。总之，这些结果确定了CAPS1在HCC发展中以前未被认识的肿瘤抑制作用。
