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

Abstract

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 β-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/β-catenin signaling pathway. Furthermore, blockage of the Wnt/β-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/β-catenin signaling pathway; it may therefore be a therapeutic target for cervical cancer.

Increased Sulfiredoxin Expression in Gastric Cancer Cells May Be a Molecular Target of the Anticancer Component Diallyl Trisulfide

“…The Srx/Prx axis has been shown to promote lung cancer maintenance and metastasis, suggesting that it could be targeted for cancer prevention and treatment [13]. Another study revealed that Srx is probably an oncoprotein in cervical cancer and that it plays an important role in the activation the Wnt/ β -catenin pathway, which is involved in cancer cell survival [14]. Similar results have been obtained in various cancer types [15].…”

“…Of course, the present study is exploratory and additional experiments are needed to confirm that Srx inhibition by DATS leads to decrease cancer cell initiation. In addition, further studies are necessary to determine the precise mechanisms being involved, but the Wnt/ β -catenin pathway is probably involved [14], as well as c-Jun, AP-1 [45], Nrf2 [34], and PI3k/Akt [46]. In addition, genetic polymorphisms could be involved in the modulation of Srx levels, such as Nrf2 polymorphisms [47].…”

An 8‑gene signature predicts the prognosis of cervical cancer following radiotherapy

“…Wei et al (30) suggested that CCDC136 negatively regulated the Wnt/β-catenin signaling pathway in zebrafish embryos. Wnt/β-catenin signaling is oncogenic and confers cancer cell proliferation, drug resistance and metastasis in various types of human cancer, including ovarian cancer and CerC (31–34) (Fig. 8).…”

LncRNA CASC11 promotes the cervical cancer progression by activating Wnt/beta-catenin signaling pathway

“…Transwell Chambers (Corning) uncoated or coated with Matrigel were used for assessing the invasion and migration of cervical cancer cells. The detailed methods were as mentioned as Lan described [14]. The migratory or invasive cells was imaged and counted utilizing an optical microscope (Carl Zeiss, Jena, Germany).…”