CAPS1 Negatively Regulates Hepatocellular Carcinoma Development through Alteration of Exocytosis-Associated Tumor Microenvironment.
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 (p= 0.003) and absence of tumor encapsulation (p= 0.016), and was associated with poor overall survival (p= 0.008) and high recurrence (p= 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.
Department of Gastroenterology and Hepatology, Shanghai Institute of Liver Diseases, Zhongshan Hospital of Fudan University, Shanghai 200032, China. xue.ruyi@zs-hospital.sh.cn.
Ruyi
R
Xue
Department of Gastroenterology and Hepatology, Shanghai Institute of Liver Diseases, Zhongshan Hospital of Fudan University, Shanghai 200032, China. wanjin1986@163.com.
Wenqing
W
Tang
Department of Gastroenterology and Hepatology, Shanghai Institute of Liver Diseases, Zhongshan Hospital of Fudan University, Shanghai 200032, China. pingdongqy@163.com.
Pingping
P
Dong
Department of Gastroenterology and Hepatology, Shanghai Institute of Liver Diseases, Zhongshan Hospital of Fudan University, Shanghai 200032, China. weng.shuqiang@zs-hospital.sh.cn.
Shuqiang
S
Weng
Department of Hepatic Surgery of Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China. 14211210033@fudan.edu.cn.
Lijie
L
Ma
Key Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032, China. shechen@fudan.edu.cn.
She
S
Chen
Department of Gastroenterology and Hepatology, Shanghai Institute of Liver Diseases, Zhongshan Hospital of Fudan University, Shanghai 200032, China. liu.taotao@zs-hospital.sh.cn.
Taotao
T
Liu
Department of Gastroenterology and Hepatology, Shanghai Institute of Liver Diseases, Zhongshan Hospital of Fudan University, Shanghai 200032, China. shen.xizhong@zs-hospital.sh.cn.
Xizhong
X
Shen
Department of Hepatic Surgery of Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China. huang.xiaowu@zs-hospital.sh.cn.
Xiaowu
X
Huang
Key Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032, China. zhangsi@fudan.edu.cn.
Si
S
Zhang
Department of Gastroenterology and Hepatology, Shanghai Institute of Liver Diseases, Zhongshan Hospital of Fudan University, Shanghai 200032, China. dong.ling@zs-hospital.sh.cn.
Ling
L
Dong
calcium-dependent activator protein for secretion 1; exocytosis; hepatocellular carcinoma; membrane trafficking; prognosis; tumor microenvironment
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