title: High GPX1 expression promotes esophageal squamous cell carcinoma invasion, migration, proliferation and cisplatin-resistance but can be reduced by vitamin D.
abstract: Esophageal cancer is one of the most common cancers worldwide. Despite recent progress in the development of novel therapies, esophageal carcinoma remains an aggressive cancer associated with a poor prognosis. The glutathione peroxidase 1 (GPX1) gene located on chromosome 3p21.3 is associated with the cancer of several organs. According to available information, GPX1, a gene downstream of NF-κB, is considered to exert adverse effects on tumour progression and enhance malignancy in some cancers but has not been reported in esophageal cancer. It is also reported that vitamin D (Vit. D), a widely used drug in the clinical setting, could suppress GPX1 expression through the NF-κB pathway. Thus, it is speculated that Vit. D could reduce malignancy in esophageal cancer by altering the NF-κB pathway. In this study, we confirmed our speculation by finding that Vit. D, through the inhibition of GPX1, decreased the migratory, invasive and proliferative capabilities, as well as cisplatin resistance, in esophageal cancer cells. Furthermore, when invasion and migration were reduced in the GPX1-inhibited cells, the expression of urokinase type plasminogen activator (uPA) and matrix metalloproteinase-2 (MMP2) was also suppressed correspondingly. Therefore, we believe that, in esophageal cancer cells, the expression of GPX1 can promote invasion, migration, proliferation and cisplatin resistance, and Vit. D can reduce the associated malignancy through the NF-κB pathway. The Vit. D- and NF-κB-mediated decrease in GPX1 expression resulted in a decrease in MMP2- and uPA-mediated invasion and migration.
authors.affiliation: Department of Thoracic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University Guangzhou 510120, P.R. China.
authors.forename: Xiangfeng
authors.initials: X
authors.lastname: Gan
authors.affiliation: Department of Thoracic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University Guangzhou 510120, P.R. China.
authors.forename: Baishen
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Thoracic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University Guangzhou 510120, P.R. China.
authors.forename: Zhuojian
authors.initials: Z
authors.lastname: Shen
authors.affiliation: Department of Pathology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University Guangzhou 510120, P.R. China.
authors.forename: Yeqing
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pathology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University Guangzhou 510120, P.R. China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Thoracic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University Guangzhou 510120, P.R. China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Xie
authors.affiliation: Department of Thoracic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University Guangzhou 510120, P.R. China.
authors.forename: Xia
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Pathology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University Guangzhou 510120, P.R. China.
authors.forename: Haigang
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Oral and Maxillofacial Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University Guangzhou 510120, P.R. China.
authors.forename: Zhiquan
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of Thoracic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University Guangzhou 510120, P.R. China.
authors.forename: Ju
authors.initials: J
authors.lastname: Chen
keywords: Esophageal squamous cell carcinoma; NF-κB; glutathione peroxidase 1; invasion; matrix metalloproteinase-2; migration; urokinase type plasminogen activator; vitamin D