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

Overview

Journal Dig Dis Sci

Specialty Gastroenterology

Date 2019 Feb 8

PMID 30730015

Citations 20

Authors

Jing Li

Yanjie Chen

Cheng Zhan

Jimin Zhu

Shuqiang Weng

Ling Dong

Taotao Liu

Xizhong Shen

Affiliations

Soon will be listed here.

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.

Citing Articles

Extracellular glypican-1 affects tumor progression and prognosis in esophageal cancer.

Shibata R, Konishi H, Arita T, Yamamoto Y, Matsuda H, Yamamoto T Cancer Med. 2024; 13(18):e70212.

PMID: 39300946 PMC: 11413415. DOI: 10.1002/cam4.70212.

Pan-cancer analysis and the oncogenic role of Glypican 1 in hepatocellular carcinoma.

Cao L, Li F, Cai S, Zhang J, Guo C, Ali S Sci Rep. 2024; 14(1):15870.

PMID: 38982153 PMC: 11233571. DOI: 10.1038/s41598-024-66838-9.

Potential markers of cancer stem-like cells in ESCC: a review of the current knowledge.

Wang L, Liu H, Liu Y, Guo S, Yan Z, Chen G Front Oncol. 2024; 13:1324819.

PMID: 38239657 PMC: 10795532. DOI: 10.3389/fonc.2023.1324819.

Glypican 1 promotes proliferation and migration in esophagogastric adenocarcinoma via activating AKT/GSK/β-catenin pathway.

Pratap A, Li A, Westbrook L, Gergen A, Mitra S, Chauhan A J Gastrointest Oncol. 2022; 13(5):2082-2104.

PMID: 36388647 PMC: 9660038. DOI: 10.21037/jgo-22-240.

Proteoglycans Determine the Dynamic Landscape of EMT and Cancer Cell Stemness.

Karagiorgou Z, Fountas P, Manou D, Knutsen E, Theocharis A Cancers (Basel). 2022; 14(21).

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