Sulfiredoxin May Promote Cervical Cancer Metastasis via Wnt/ß-Catenin Signaling Pathway.

The abnormal elevation of sulfiredoxin (Srx/SRXN1)-an antioxidant enzyme whose main function is to protect against oxidative stress-has been shown to be closely correlated with the progression of several types of cancer, including human cervical cancer. However, the molecular mechanism by which Srx promotes tumor progression, especially cancer metastasis in cervical cancer, has not been elucidated. Here, we show that Srx expression gradually increases during the progression of human cervical cancer and its expression level is closely correlated with lymph node metastasis. Our study also reveals a significant positive correlation between the expression of Srx and ß-catenin in cervical cancer tissues. Loss-of-function studies demonstrate that Srx knockdown using a lentiviral vector-mediated specific shRNA decreases the migration and invasion capacity in HeLa (human papilloma virus 18 type cervical cancer cell line) and SiHa SiHa (cervical squamous cancer cell line). Notably, the exact opposite effects were observed in gain-of-function experiments in C-33A cells. Mechanistically, downregulation or upregulation of Srx leads to an altered expression of proteins associated with the Wnt/ß-catenin signaling pathway. Furthermore, blockage of the Wnt/ß-catenin signaling pathway contributed to attenuated Srx expression and resulted in significant inhibition of cell migration and invasion in cervical cancer cell lines. Combined, Srx might be an oncoprotein in cervical cancer, playing critical roles in activating the Wnt/ß-catenin signaling pathway; it may therefore be a therapeutic target for cervical cancer.

[Highly expressed sulfiredoxin and ß-catenin are associated with malignancy of cervical squamous cell carcinoma].

Objective To investigate the expressions of sulfiredoxin (Srx) and ß-catenin in human cervical squamous cell carcinoma (CSCC) and their clinical significance. Methods Immunohistochemistry was used to detect the expressions of Srx and ß-catenin in human cervical specimens, including normal cervical squamous cell epithelium tissues (NC), cervical intraepithelial neoplasia tissues (CIN), and CSCC. The correlation between Srx expression and ß-catenin expression and the relationship of the two proteins to clinical the pathological features of cervical cancer were analyzed. Results The expression of Srx in CIN and CSCC was significantly higher than that in NC. In addition, Srx and ß-catenin expressions were positively correlated to CSCC tissues. Furthermore, the up-regulated expression of Srx was significantly associated with lymph node metastasis, infiltration of vessels, and the depth of cancer invasion. However, its expression was not associated with age, tumor size, degree of differentiation, and International Federation of Gynecology and Obstetrics (FIGO) grade. Finally, the overexpression of ß-catenin was significantly correlated with lymph node metastasis, degree of differentiation, and FIGO grade. However, ß-catenin expression was not correlated with age, tumor size, and the depth of cancer invasion. Conclusion Srx and ß-catenin are highly expressed in CSCC and associated with malignancy.