J Cancer 2018; 9(21):3939-3949. doi:10.7150/jca.26041 This issue
1. School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou 215123, China
2. State Key Laboratory of Radiation Medicine and Protection, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China
3. Suzhou Cancer Center Core Laboratory, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou 215001, China
4. Department of Gastroenterology, First People's Hospital of Xuzhou, Xuzhou 221002, China
5. Department of Radiotherapy, Changzhou Tumor Hospital, Soochow University, Changzhou 213032, China
6. Department of Oncology, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou 213100, China
# The first two authors contributed equally to this work.
Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies. Peroxiredoxin 6 (PRDX6), a member of peroxidase superfamily, has a function of eliminating the reactive oxygen species (ROS), and participates in development of multiple diseases, including tumors. The purpose of this study was to investigate the expression of PRDX6 in normal and cancerous esophageal tissues and to characterize its role in ESCC progression. We found significantly higher expression of PRDX6 in ESCC tissues than in normal esophageal tissues or tumor-adjacent tissues and that the PRDX6 expression level was positively correlated with the proliferation-related markers. In ESCC cells, PRDX6 distribution was more pronounced in the nucleus region. PRDX6 overexpression by an adenovirus significantly promoted cell proliferation, migration and invasion in TE-1 and Eca-109 cells. Conversely, lentivirus-mediated knock-down of PRDX6 expression significantly reduced cell growth, colony formation and metastasis in ESCC cells. PRDX6 modulated the phosphorylation of Akt and Erk1/2, and the expression of MMP2. We also found that PRDX6 and Erk1/2 pathway were mutually regulated in ESCC cells. In addition, PRDX6 overexpression eliminated radiation-induced ROS and decreased consequent cell apoptosis, indicative of a role in radioresistance. Finally, the role of PRDX6 in promoting tumor growth was further confirmed in nude mice with ESCC xenografts. Taken together, we demonstrated that overexpression of PRDX6 promotes the progression of ESCC through Erk1/2, which provides a potential therapeutic target for human ESCC.
Keywords: cell proliferation, esophageal squamous cell carcinoma (ESCC), MAP kinase signaling system, reactive oxygen species (ROS), Peroxiredoxin 6 (PRDX6)