PAI-1 overexpression promotes invasion and migration of esophageal squamous carcinoma cells.

Abstract

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide. Plasminogen activator inhibitor-1 (PAI-1), encoded by SERPINE1, is highly expressed in various types of tumor tissues, which contributes to cancer progression. The present study explored the role and underlying mechanisms of PAI-1 in ESCC. We found that the PAI-1 protein was extracellularly secreted more from ESCC cells with high PAI-1 expression using Western blotting and enzyme linked immunosorbent assay (ELISA). Knockdown of SERPINE1 expression significantly inhibited the invasion and migration of ESCC KYSE150 and KYSE450 cell lines, which could be restored when adding exogenous human recombinant PAI-1 into the culture medium of the cells stably expressing SERPINE1 shRNA. In vivo experiments showed that SERPINE1 knockdown significantly inhibited xenograft growth and lung metastasis of ESCC cells. Molecular analysis demonstrated that PAI-1 activated AKT and ERK signaling pathways. Co-immunoprecipitation (Co-IP) assays identified that PAI-1 may interact with the membrane receptor LDL receptor related protein 1 (LRP1). These results indicated that overexpression of PAI-1, through interacting with LRP1, might enhance invasion and migration of ESCC cells as well as promote ESCC progression.

• Authors: Di Wang, Li Yan Yang, Zou Liu, Jing Yu, Min Jie Zhang, Yu Zhang, Yan Cai, Xin Xu, Jia Jie Hao, Ming Rong Wang
• Journal: Yi chuan = Hereditas (Yi Chuan) Vol. 42 Issue 3 Pg. 287-295 (Mar 20 2020) ISSN: 0253-9772 [Print] China
• PMID: 32217514 (Publication Type: Journal Article)

Chemical References

• LRP1 protein, human
• Low Density Lipoprotein Receptor-Related Protein-1
• Plasminogen Activator Inhibitor 1
• Recombinant Proteins
• SERPINE1 protein, human

Topics

• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Esophageal Neoplasms (genetics, pathology)
• Esophageal Squamous Cell Carcinoma (genetics, pathology)
• Gene Expression Regulation, Neoplastic
• Humans
• Low Density Lipoprotein Receptor-Related Protein-1 (metabolism)
• Neoplasm Invasiveness
• Plasminogen Activator Inhibitor 1 (genetics)
• Recombinant Proteins (genetics)