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.
Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Dig Dis Sci. 2019 Jun;64(6):1493-1502. doi: 10.1007/s10620-019-5461-9. Epub 2019 Feb 7.
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).
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.
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.
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.
磷脂酰肌醇聚糖蛋白-1（GPC1）是一种细胞表面硫酸乙酰肝素蛋白聚糖，可促进多种人类癌症的发病机制。本研究重点研究 GPC1 在促进食管鳞状细胞癌（ESCC）细胞增殖和运动中的作用。
采用免疫组织化学（IHC）法检测 248 例 ESCC 患者肿瘤组织中 GPC1 的表达和分布。通过细胞计数（试剂盒-8）、流式细胞术、Transwell、划痕愈合、IHC 和 Western blot 实验来研究 GPC1 增强细胞增殖和运动性的分子机制。
ESCC 肿瘤组织中 GPC1 的水平高于癌旁组织（IHC 评分：5.42±2.15 对 0.86±0.96）。在 EC9706 细胞中异位过表达 GPC1 可促进细胞生长和 G1/S 期转变；相反，在 Eca109 细胞中敲低 GPC1 可减弱细胞增殖并诱导 G2/M 期阻滞。此外，GPC1 的上调增强了 ESCC 细胞的迁移能力并诱导上皮间质转化（EMT），表现为 EMT 标志物的异常表达。在机制上，我们证明 GPC1 通过上调 p-Akt 和β-catenin 并降低 ESCC 中的 PTEN 表达来增加 GPC1 水平。
本研究表明，GPC1 通过调节 PTEN/Akt/β-catenin 通路促进 ESCC 细胞的侵袭性增殖。GPC1 可能是 ESCC 治疗的一个有前途的靶点。
