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Glypican-1 Promotes Tumorigenesis by Regulating the PTEN/Akt/β-Catenin Signaling Pathway in Esophageal Squamous Cell Carcinoma

  • Jing Li
  • Yanjie Chen
  • Cheng Zhan
  • Jimin Zhu
  • Shuqiang Weng
  • Ling Dong
  • Taotao Liu
  • Xizhong ShenEmail author
Original Article
  • 13 Downloads

Abstract

Background and Aims

Glypican-1 (GPC1), a cell-surface heparan sulfate proteoglycan, promotes the pathogenesis of many human cancers. This study focuses on the role of GPC1 in the promotion of cell proliferation and motility in esophageal squamous cell carcinoma (ESCC).

Methods

The expression and distribution of GPC1 were measured in tumor tissues from 248 ESCC patients using immunohistochemical (IHC) assays. Cell counting (kit-8), flow cytometry, Transwell, wound healing, IHC, and Western blotting assays were performed to examine the molecular mechanisms that underlie how GPC1 enhances cell proliferation and motility.

Results

The level of GPC1 was higher in ESCC tumor samples than in para-tumor tissues (IHC score: 5.42 ± 2.15 vs. 0.86 ± 0.96). Ectopic overexpression of GPC1 in EC9706 cells promoted cell growth and the G1/S phase transition; conversely, GPC1 knockdown in Eca109 cells attenuated cell proliferation and induced G2/M phase arrest. In addition, GPC1 upregulation enhanced ESCC cell motility and induced epithelial mesenchymal transition (EMT), as demonstrated by the aberrant expression of EMT markers. Mechanistically, we demonstrated that GPC1 increased levels of p-Akt and β-catenin and reduced PTEN expression in ESCC.

Conclusions

Our study indicated that GPC1 promotes the aggressive proliferation of ESCC cells by regulating the PTEN/Akt/β-catenin pathway. GPC1 may be a promising target for ESCC treatment.

Keywords

Glypican-1 Esophageal squamous cell carcinoma Cell proliferation Epithelial–mesenchymal transition PTEN/Akt/β-Catenin signaling pathway 

Notes

Acknowledgments

This work was sponsored by Shanghai Sailing Program (No. 16YF1401500), National Nature Science Foundation of China (Nos. 81301820, 81472673, 81672720, 81672334), the Fund of Shanghai Science and Technology Commission(16ZR1406100), and the National Clinical Key Special Subject of China.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Jing Li
    • 1
  • Yanjie Chen
    • 1
  • Cheng Zhan
    • 2
  • Jimin Zhu
    • 1
  • Shuqiang Weng
    • 1
  • Ling Dong
    • 1
  • Taotao Liu
    • 1
  • Xizhong Shen
    • 1
    Email author
  1. 1.Department of Gastroenterology, Zhongshan Hospital, Key Laboratory of Medical Molecule Virology, Ministry of Education and Health, Shanghai Institute of Liver DiseasesFudan UniversityShanghaiChina
  2. 2.Department of Thoracic SurgeryZhongshan Hospital, Fudan UniversityShanghaiChina

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