Research Papers:

RRAD inhibits the Warburg effect through negative regulation of the NF-κB signaling

Juan Liu, Cen Zhang, Rui Wu, Meihua Lin, Yingjian Liang, Jia Liu, Xiaolong Wang, Bo Yang and Zhaohui Feng _

PDF  |  HTML  |  How to cite

Oncotarget. 2015; 6:14982-14992. https://doi.org/10.18632/oncotarget.3719

Metrics: PDF 2540 views  |   HTML 2394 views  |   ?  


Juan Liu1,*, Cen Zhang1,*, Rui Wu1,2, Meihua Lin1, Yingjian Liang1, Jia Liu1, Xiaolong Wang1, Bo Yang2, and Zhaohui Feng1

1 Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers, State University of New Jersey, New Brunswick, NJ, USA

Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China

* These authors have contributed equally to this work

Correspondence to:

Zhaohui Feng, email:

Keywords: RRAD, the Warburg effect, NF-κB, p65, GLUT1

Received: January 29, 2015 Accepted: March 05, 2015 Published: March 30, 2015


Cancer cells preferentially use aerobic glycolysis to meet their increased energetic and biosynthetic demands, a phenomenon known as the Warburg effect. Its underlying mechanism is not fully understood. RRAD, a small GTPase, is a potential tumor suppressor in lung cancer. RRAD expression is frequently down-regulated in lung cancer, which is associated with tumor progression and poor prognosis. Recently, RRAD was reported to repress the Warburg effect, indicating that down-regulation of RRAD expression is an important mechanism contributing to the Warburg effect in lung cancer. However, the mechanism by which RRAD inhibits the Warburg effect remains unclear. Here, we found that RRAD negatively regulates the NF-κB signaling to inhibit the GLUT1 translocation and the Warburg effect in lung cancer cells. Mechanically, RRAD directly binds to the p65 subunit of the NF-κB complex and inhibits the nuclear translocation of p65, which in turn negatively regulates the NF-κB signaling to inhibit GLUT1 translocation and the Warburg effect. Blocking the NF-κB signaling largely abolishes the inhibitory effects of RRAD on the translocation of GLUT1 to the plasma membrane and the Warburg effect. Taken together, our results revealed a novel mechanism by which RRAD negatively regulates the Warburg effect in lung cancer cells.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 3719