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Hereditas(Beijing) ›› 2020, Vol. 42 ›› Issue (3): 287-295.doi: 10.16288/j.yczz.19-334

• Research Article • Previous Articles     Next Articles

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

Di Wang, Liyan Yang, Zou Liu, Jing Yu, Minjie Zhang, Yu Zhang, Yan Cai, Xin Xu, Jiajie Hao(), Mingrong Wang()   

  1. State Key Laboratory of Molecular Oncology, Center for Cancer Precision Medicine, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
  • Received:2019-12-31 Revised:2020-02-12 Online:2020-03-20 Published:2020-02-27
  • Contact: Hao Jiajie,Wang Mingrong E-mail:hjj8173@126.com;wangmr2015@126.com
  • Supported by:
    Supported by the National Natural Science Foundation of China No(81520108023);CAMS Innovation Fund for Medical Sciences Nos(2019-I2M-1-003);CAMS Innovation Fund for Medical Sciences Nos(2016-I2M-3-007);Beijing Nova Program No(Z171100001117017)

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.

Key words: PAI-1, ESCC, invasion, migration