在日本的东京大学、美国的国立癌症研究所（NCI/NIH）、约翰霍普金斯大学医学院以及中国科学技术大学从事肿瘤学的研究，致力于解析肿瘤代谢异常和肿瘤微环境因素的相互关系及抗肿瘤药物的研发,研究成果发表于Cancer Cell, PNAS, Nature Communications, Cell Reports, Cell Research, Angew Chem Int Ed Engl. 等期刊上，这些工作系统地揭示了在肿瘤微环境中，肿瘤细胞如何适应低氧、营养匮乏等应激状态而生存并通过代谢改变等来促进肿瘤的增殖和发展，产生了较为广泛的影响。
Cancer cells rewire metabolic pathways to obtain sufficient energy or building blocks to support rapid cell growth and proliferation . Hypoxia and nutrition deprivation are central characterictics of tumor microenvironment. In this presentation, I will discuss our recent findings that, while cancer cells are known to consume glucose, glutamine and fatty acids for energy as well as carbon and nitrogen sources for anabolism, under nutrition deprivation conditions, they also reprogram their metabolic pathways by seeking alternative nutrient sources to meet the demands for proliferation. Specifically, we discovered that catabolism of ketone bodies, which are produced in the liver but not consumed by normal adult liver cells, is re-activated in hepatocellular carcinoma (HCC) cells under nutrition deprivation conditions. Mechanistically, 3-oxoacid-CoA transferase enzyme (OXCT1), a rate-limiting ketolytic enzyme whose expression is suppressed in normal adult liver tissues, is re-induced for energy production under nutrition deprivation conditions in HCC cells. Analysis of clinical HCC samples reveals that increased OXCT1 expression predicts higher patient mortality. Taken together, we uncover here a novel metabolic adaptation by which nutrition-stressed HCC cells employ ketone bodies for cancer progr.