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CAPS1 Negatively Regulates Hepatocellular Carcinoma Development through Alteration of Exocytosis-Associated Tumor
Ruyi Xue1, Wenqing Tang2, Pingping Dong3
1Department of Gastroenterology and Hepatology, Shanghai Institute of Liver Diseases, Zhongshan Hospital of Fudan University, Shanghai 200032, China. xue.ruyi@zs-hospital.sh.cn.
Abstract:
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.
Insights
Calcium-dependent activator protein for secretion 1 (CAPS1) acts as a tumor suppressor in hepatocellular carcinoma (HCC). Loss of CAPS1 correlates with aggressive HCC, while its overexpression inhibits tumor growth and proliferation.
Area of Science:
- Oncology
- Cell Biology
- Molecular Neuroscience
Background:
- Calcium-dependent activator protein for secretion 1 (CAPS1) is crucial for dense-core vesicle (DCV) exocytosis in neurons and neuroendocrine cells.
- The function of CAPS1 in cancer, particularly hepatocellular carcinoma (HCC), is not well understood.
Purpose of the Study:
- To investigate the role of CAPS1 in the development and progression of hepatocellular carcinoma (HCC).
- To evaluate CAPS1 expression levels and its prognostic significance in HCC patients.
Main Methods:
- Quantified CAPS1 expression in eight hepatoma cell lines and 141 HCC patient specimens.
- Assessed the correlation between CAPS1 expression and clinical parameters, including tumor grade and metastasis.
- Investigated the functional impact of CAPS1 overexpression on hepatoma cell proliferation, migration, and tumor growth in vitro and in vivo models.
Main Results:
- Reduced CAPS1 expression in HCC tissues significantly correlated with advanced tumor-node-metastasis (TNM) stage and lack of tumor encapsulation.
- Lower CAPS1 levels were associated with poorer overall survival and increased recurrence rates in HCC patients.
- Overexpression of CAPS1 suppressed hepatoma cell proliferation and migration in vitro and inhibited xenograft tumor growth in vivo, suggesting modulation of the tumor microenvironment.
Conclusions:
- CAPS1 functions as a tumor suppressor in hepatocellular carcinoma.
- CAPS1 expression is a potential prognostic biomarker for HCC.
- Targeting CAPS1 or its pathways may offer therapeutic strategies for HCC.
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