Research Paper Volume 16, Issue 19 pp 12806—12819

FGA influences invasion and metastasis of hepatocellular carcinoma through the PI3K/AKT pathway

Xi Han1, , Zefeng Liu1, , Mengying Cui1, , Jie Lin1, , Yongzhi Li1, , Hanjiao Qin2, , Jiyao Sheng1, , Xuewen Zhang1, ,

  • 1 Department of Hepatobiliary and Pancreatic Surgery, Second Hospital of Jilin University, Changchun, Jilin 130041, China
  • 2 Department of Radiotherapy, Second Hospital of Jilin University, Changchun, Jilin 130041, China

Received: November 17, 2023       Accepted: June 3, 2024       Published: July 9, 2024      

https://doi.org/10.18632/aging.206011
How to Cite

Copyright: © 2024 Han et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Fibrinogen is an important plasma protein composed of three polypeptide chains, fibrinogen alpha (FGA), beta, and gamma. Apart from being an inflammation regulator, fibrinogen also plays a role in tumor progression. Liver cancer usually has a poor prognosis, with chronic hepatitis being the main cause of liver cirrhosis and hepatocellular carcinoma (HCC). FGA serves as a serological marker for chronic hepatitis, but its relationship with liver cancer remains unclear. Through bioinformatics analysis and agarose gel electrophoresis, we found that FGA was downregulated in HCC and correlated with tumor stage and grade. By constructing both FGA gene knockout and overexpression cell models, we demonstrated that overexpressing FGA inhibited migration and invasion of liver cancer cells through Transwell migration/invasion and wound healing assays. Western blotting experiments showed that FGA overexpression increased the expression of the epithelial-mesenchymal transition marker protein E-cadherin while decreasing N-cadherin and slug protein expression. In addition, FGA knockout activated the PI3K/AKT pathway. In a mouse model of metastatic tumors, overexpression of FGA restricted the spread of tumor cells. In conclusion, FGA exhibits an inhibitory effect on tumor metastasis, providing new insights for the treatment of advanced HCC metastatic tumors.

Abbreviations

FGA: Fibrinogen alpha; HCC: Hepatocellular carcinoma; FGB: Fibrinogen gamma; FGG: Fibrinogen gamma; EMT: Epithelial-mesenchymal transition; LUAD: Lung adenocarcinoma; ECM: Extracellular matrix.