Glucose-dependent acetylation of Rictor promotes targeted cancer therapy resistance

• DOI: 10.1073/pnas.1511759112
• Publication Date: 2015-07-14T02:45:12Z
• Authors: Kenta Masui; Kazuhiro Tanaka; Shiro Ikegami; Genaro R. Villa; Huijun Yang; William H. Yong; Timothy F. Cloughesy; Kanato Yamagata; Nobutaka Arai; Webster K. Cavenee; Paul S. Mischel
• Keywords: Targeted Therapy

Significance Cancer cells reprogram their metabolism in response to growth factor receptor mutations. However, the effect of altered nutrient levels on oncogenic signaling and therapeutic is not well understood. We demonstrate that glucose or acetate, two abundant “fuel” sources brain, promote epidermal vIII (EGFRvIII)-dependent through activation mechanistic target rapamycin complex 2 (mTORC2) by acetylation its core component Rictor. This activity mediated elevated acetyl-CoA. A surprising implication this study acetate can contribute targeted therapy resistance maintaining downstream components cascade.