scholarly journals Activated hepatic stellate cells play pivotal roles in hepatocellular carcinoma cell chemoresistance and migration in multicellular tumor spheroids

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Yeonhwa Song ◽  
Se-hyuk Kim ◽  
Kang Mo Kim ◽  
Eun Kyung Choi ◽  
Joon Kim ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatic Stellate Cells ◽  
Carcinoma Cell ◽  
Stellate Cells ◽  
Multicellular Tumor Spheroids ◽  
Tumor Spheroids ◽  
Hepatocellular Carcinoma Cell ◽  
Activated Hepatic Stellate Cells ◽  
And Migration

scholarly journals GJA1 promotes hepatocellular carcinoma progression by mediating TGF-β-induced activation and the epithelial–mesenchymal transition of hepatic stellate cells

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 1459-1471
Author(s):  
Gengming Niu ◽  
Xiaotian Zhang ◽  
Runqi Hong ◽  
Ximin Yang ◽  
Jiawei Gu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Conditioned Medium ◽  
Hepatic Stellate Cells ◽  
Hepatic Cirrhosis ◽  
Epithelial Mesenchymal Transition ◽  
Stellate Cells ◽  
Gene Set Enrichment Analysis ◽  
Mesenchymal Transition ◽  
And Migration ◽  
Proliferation And Migration

Abstract Introduction Gap junction protein, alpha 1 (GJA1), which is correlated with recurrences and unfavorable prognoses in hepatocellular carcinomas (HCCs), is one of the specific proteins expressed by activated hepatic stellate cells (HSCs). Methods Expression of GJA1 was compared between HCCs and nontumor tissues (NTs), between hepatic cirrhosis and NTs, and between primary and metastatic HCCs using transcriptomic datasets from the Gene Expression Omnibus and the Integrative Molecular Database of Hepatocellular Carcinoma. The in vitro activities of GJA1 were investigated in cultured HSCs and HCC cells. The underlying mechanism was characterized using Gene Set Enrichment Analysis and validated by western blotting. Results The expression of GJA1 was significantly increased in HCCs and hepatic cirrhosis compared to that in NTs. GJA1 was also overexpressed in pulmonary metastases from HCCs when compared with HCCs without metastasis. Overexpression of GJA1 promoted while knockdown of GJA1 inhibited proliferation and transforming growth factor (TGF)-β-mediated activation and migration of cultured HSCs. Overexpression of GJA1 by lentivirus infection promoted proliferation and migration, while conditioned medium from HSCs overexpressing GJA1 promoted migration but inhibited proliferation of Hep3B and PLC-PRF-5 cells. Lentivirus infection with shGJA1 or conditioned medium from shGJA1-infected HSCs inhibited the proliferation and migration of HCCLM3 cells that had a high propensity toward lung metastasis. Mechanistically, GJA1 induced the epithelial–mesenchymal transition (EMT) in HSCs and HCCLM3 cells. Conclusion GJA1 promoted HCC progression by inducing HSC activation and the EMT in HSCs. GJA1 is potentially regulated by TGF-β and thus may be a therapeutic target to inhibit HCC progression.

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