Glutaredoxin 3 promotes nasopharyngeal carcinoma growth and metastasis via EGFR/Akt pathway and independent of ROS

Abstract

Glutaredoxin 3 (GLRX3) is antioxidant enzyme, maintaining a low level of ROS, thus contributing to the survival and metastasis of several types of cancer. However, the expression and functions of GLRX3 have not been addressed in nasopharyngeal carcinoma (NPC). In this study, we found that GLRX3 was overexpressed in NPC. Knockdown of GLRX3 in NPC cell lines inhibited proliferation in vitro, tumorignesis in vivo, and colony formation. In addition, GLRX3 knockdown decreased the migration and invasion capacity of NPC cells by reversing the epithelial-mesenchymal transition (EMT). Furthermore, stabilization of GLRX3 was positively related to with epidermal growth factor receptor (EGFR) expression and negatively with ROS generation. Phosphorylation of Akt, a key downstream effector, was induced by EGFR signaling but did not rely on increasing ROS level in NPC cells. GLRX3 might be an oncoprotein in NPC, playing important roles in increasing redox reaction and activating EGFR/ Akt signals, so it may be a therapeutic target for NPC.

Inactivation of HMGCL promotes proliferation and metastasis of nasopharyngeal carcinoma by suppressing oxidative stress

“…A recent study reported that increased ROS production could trigger the reactivation of EBV from latency in NPC cells 48 . We also showed that knocking down a reductase, GLRX3, impaired the proliferation and metastasis of NPC cells by elevating the level of ROS 39 . Hence, inhibition of ketongenesis by downregulating HMGCL may be one of the mechanisms involved in modulating EBV latent infection in NPC cells, thus contributing to tumorigenesis and progression by reducing the immunogenicity of NPC cells.…”

“…A metabolic shift, including glycolysis and ROS generation, contributes to NPC metastasis 38 , 39 . To investigate the role of HMGCL in the metastatic potential of NPC cells, we used 2D and 3D model systems to determine the capacity for migration and invasion, respectively.…”

Glibenclamide, a diabetic drug, prevents acute radiation-induced liver injury of mice via up-regulating intracellular ROS and subsequently activating Akt-NF-κB pathway

“…As ROS is the crucial mediator to radiation injury[ 6 ], we originally hypothesize that glibenclamide should reduce ROS to protect hepatocyte from radiation. Despite this perplexing result, some studies, indeed have reported that modest ROS could induce Akt and NF-κB activation to enhance cells survival [ 25 – 28 ]. Therefore we speculated that pre-treatment of glibenclamide might moderately up-regulate intracellular ROS level and subsequently activate Akt–NF-κB pathway to enhance hepatocyte survival against radiation.…”

Stable knockdown of ZBTB7A promotes cell proliferation and progression in nasopharyngeal carcinoma

“…The tumor metastasis related factors, such as Epstein-Barr virus (5), tumor metastatic genes, tumor metastatic suppressor genes (6-8), cell adhesion molecules (9), and noncoding RNAs (10-12), play important roles in regulating the metastatic mechanisms of NPC. These factors contribute to create a complex network of regulation, which can promote or suppress the metastasis of NPC (13-15).…”