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

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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.

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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.

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Author notes

  1. Jing Li and Yanjie Chen have contributed equally to this work.

Authors and Affiliations

  1. Department of Gastroenterology, Zhongshan Hospital, Key Laboratory of Medical Molecule Virology, Ministry of Education and Health, Shanghai Institute of Liver Diseases, Fudan University, Shanghai, 200032, China

    Jing Li, Yanjie Chen, Jimin Zhu, Shuqiang Weng, Ling Dong, Taotao Liu & Xizhong Shen

  2. Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China

    Cheng Zhan

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  1. Jing Li
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Correspondence to Xizhong Shen.

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Li, J., Chen, Y., Zhan, C. et al. Glypican-1 Promotes Tumorigenesis by Regulating the PTEN/Akt/β-Catenin Signaling Pathway in Esophageal Squamous Cell Carcinoma. Dig Dis Sci 64, 1493–1502 (2019). https://doi.org/10.1007/s10620-019-5461-9

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