时　间：2020年9月15日上午11:30

地　点：高等研究院530会议室

报告人：张义磊，美国德克萨斯大学 MD 安德森癌症中心，讲师

报告题目：Metabolic regulation of ferroptosis and glucose dependency in tumor suppression

报告简介：

Ferroptosis is a type of regulated cell death induced by iron-dependent lipid peroxidation. Since reported in 2012, ferroptosis has been widely discovered to play important roles in many physiological and pathological conditions, such as ischemia-reperfusion injury, neurodegenerative disease and tumor suppression. Dr. Zhang demonstrates that BAP1, a frequently mutated tumor suppressor gene found in a variety of cancer types, epigenetically suppresses SLC7A11 gene expression through decreasing H2Aub level and promotes ferroptosis, which is involved in the tumor-suppressive function of BAP1. In addition, Dr. Zhang and his collogues also found that ferroptosis is involved in irradiation-mediated tumor suppression, which provides therapeutic potential through combining ferroptosis-inducing reagents and irradiation in cancer treatment.

Dysregulated metabolism is one of the hallmarks of cancer. Tumor cells rewire metabolic pathways to meet their large demands of nutrients during uncontrolled growth and adapting various stress conditions within the body. Glucose is one of the major nutrients required for tumor cell growth and survival, therefore tumor cells are always considered to be addicted to glucose and targeting glucose transporters (GLUTs) remains to be of great interest in cancer therapy. Dr. Zhang and his colleagues find that in cancer cells with high SLC7A11 expression and cystine uptake, cystine reduction to cysteine consumes lots of NADPH, which make cells more dependent on glucose/PPP to generate NADPH and expose a metabolic vulnerability in tumor

therapy.