Jing Li1, Yanjie Chen1, Cheng Zhan2, Jimin Zhu1, Shuqiang Weng1, Ling Dong1, Taotao Liu1, Xizhong Shen3. 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. 2. Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. 3. 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. shen.xizhong@zs-hospital.sh.cn.
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.
BACKGROUND AND AIMS: Glypican-1 (GPC1), a cell-surface heparan sulfate proteoglycan, promotes the pathogenesis of many humancancers. 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.
Authors: Jingjing Qi; Yong Yu; Özlem Akilli Öztürk; Jane D Holland; Daniel Besser; Johannes Fritzmann; Annika Wulf-Goldenberg; Klaus Eckert; Iduna Fichtner; Walter Birchmeier Journal: Gut Date: 2015-07-08 Impact factor: 23.059
Authors: G Murphy; V McCormack; B Abedi-Ardekani; M Arnold; M C Camargo; N A Dar; S M Dawsey; A Etemadi; R C Fitzgerald; D E Fleischer; N D Freedman; A M Goldstein; S Gopal; M Hashemian; N Hu; P L Hyland; B Kaimila; F Kamangar; R Malekzadeh; C G Mathew; D Menya; G Mulima; M M Mwachiro; A Mwasamwaja; N Pritchett; Y-L Qiao; L F Ribeiro-Pinto; M Ricciardone; J Schüz; F Sitas; P R Taylor; K Van Loon; S-M Wang; W-Q Wei; C P Wild; C Wu; C C Abnet; S J Chanock; P Brennan Journal: Ann Oncol Date: 2017-09-01 Impact factor: 32.976