Qiou Wei
University of Kentucky College of Medicine, USA
Title: Targeting sulfiredoxin in colorectal cancer
Biography
Biography: Qiou Wei
Abstract
Colorectal cancer is the third most common cancer and the second leading cause of cancer death in both men and women. Sulfiredoxin (Srx) is a unique reductase that restores the peroxidase activity of peroxiredoxins (Prxs) by reducing the hyperoxidized, inactive form of Prxs back to their active, reduced form. To understand the role and mechanism of Srx in colorectal cancer development, we studied the functional significance of Srx in colon tumorigenesis, cancer invasion and metastasis using human patient primary specimens, cell culture as well as mouse models. We demonstrate that Srx is highly expressed in primary specimens of human colorectal cancer patients, and such abnormally high expression of Srx enhances cancer invasion in culture and drives cancer metastasis in a mouse orthotopical implantation model. Moreover, we also demonstrate that genetic depletion of Srx protects mouse from carcinogen-induced colon cancer development. Mechanistically, we reveal that loss of Srx sensitizes cancer cell to oxidative stress induced cell death, whereas the presence of Srx enhances the activation of mitogen activated protein kinase signaling through increasing the C-terminal tyrosine phosphorylation levels of the epidermal growth factor receptor (EGFR). This function of Srx is mediated through its inhibition of EGFR acetylation, a novel post-translational modification of EGFR in human CRC cells identified by liquid chromatography-electrospray ionization-tandem mass spectrometry analysis. Taken together, our data suggest that Srx promotes CRC cell invasion and metastasis through a novel mechanism of enhancing EGFR signaling, and it may thus be used as a potential target to develop molecular therapeutics for the treatment of colorectal cancer in patients.