J Cancer 2019; 10(23):5681-5688. doi:10.7150/jca.32986 This issue

Research Paper

Panx1 promotes invasion-metastasis cascade in hepatocellular carcinoma

Guangjun Shi1,*, Chuanliang Liu2,*, Yiming Yang3,*, Liwei Song4, Xueni Liu4, Chuanxu Wang1, Zhihai Peng4, Hao Li4✉, Lin Zhong4✉

1. Department of Hepatobiliary Surgery, The Affiliated Qingdao Municipal Hospital of Qingdao University, Qingdao, China.
2. Department of General Surgery, The Third People's Hospital of LinYi, Linyi, China.
3. School of Life Science, Shanghai University, Shanghai, China.
4. Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
*These authors contributed equally to this work.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Shi G, Liu C, Yang Y, Song L, Liu X, Wang C, Peng Z, Li H, Zhong L. Panx1 promotes invasion-metastasis cascade in hepatocellular carcinoma. J Cancer 2019; 10(23):5681-5688. doi:10.7150/jca.32986. Available from https://www.jcancer.org/v10p5681.htm

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Background: The molecular function of pannexin1 (Panx1) in different tumor types has been remained equivocal. Until now, there is no study focused on the function of panx1 in hepatocellular carcinoma (HCC). This study aimed to explore the role of Panx1 in the invasion and metastasis of HCC.

Methods: The expressions of Panx1 in 126 cases of HCC were analyzed by immunohistochemistry (IHC). The effects of Panx1 on HCC cell metastasis and invasion were observed by transwell. The expression levels of Panx1 and epithelial-mesenchymal transition (EMT) related proteins in HCC cells and tissues were detected by western blot and IHC. The tumor metastatic abilities were compared between Panx1 knockout mice and nude mice.

Results: The higher expression of Panx1 in HCC was positively correlated with tumor lymph node metastasis, TNM (tumor, node, metastasis) classification and poor prognosis (overall survival, hazard ratio [HR] 2.769, 95% confidence interval [95%CI] 1.528-5.017, P=0.001; disease-free survival, HR=2.344, 95%CI 1.473-3.730, P<0.001). Overexpression of Panx1 promoted invasion and migration of HCC cells through modulation of EMT in vitro and in vivo.

Conclusions: Our results suggest that the high expression of Panx1 is associated with poor HCC prognosis, providing a new clue for effective intervention for HCC metastasis.

Keywords: Panx1, hepatocellular carcinoma, metastasis, EMT