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上海市肿瘤研究所--郝宇钧

郝宇钧
郝宇钧 研究员

上海市肿瘤研究所

【个人简介】

研究员,博士生导师。2009年博士毕业于中国科学院遗传与发育生物学研究所;2009年至2017年在美国凯斯西储大学博士后进修;2017年归国就职于上海交通大学医学院附属仁济医院上海市肿瘤研究所,现为肿瘤代谢研究组课题组长。先后入选上海市东方学者特聘教授、上海市优秀学科带头人、上海交通大学医学院双百人等人才计划。曾以第一作者或通讯作者在Cancer Cell, Nature Communications, Journal of Experimental & Clinical Cancer Research, Scientific Reports等杂志发表论文。

精彩报告

2020-11-03 “肿瘤代谢与微环境”主题网络研讨会(2020)
报告:Targeting glutamine metabolism in mutated-PIK3CA colorectal cancer 报名占位
【摘要】 PIK3CA, which encodes the p110α catalytic subunit of phosphatidylinositol 3-kinase α, is one of the most frequently mutated oncogene in human cancers. Here we show that oncogenic PIK3CA mutations reprogram glutamine metabolism by up-regulating glutamate pyruvate transaminase 2 (GPT2) in colorectal cancer (CRC) cells through an AKT-independent PDK1-RSK2-ATF4 signaling axis, thereby rendering them addicted to glutamine. With [U-13C5]glutamine flux tracing in colorectal cancer (CRC) models in vitro and in vivo, PIK3CA mutations significantly enhance glutamine metabolism into TCA cycle in tumors comparing with normal colon tissues or PIK3CA Wild-type tumors. Glutamine metabolism inhibitors CB-839 or AOA preferentially inhibits xenograft growth of PIK3CA mutant, but not PIK3CA wild-type, CRCs. Moreover, combination of CB-839 with 5-FU induces CRC tumor regression. These data suggest that CRC utilize glutamine to replenish the TCA cycle and that targeting glutamine metabolism may be an effective approach to treat PIK3CA mutant CRCs.

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