Nuclear translocation of metabolic enzyme PKM2 participates in high glucose-promoted HCC metastasis by strengthening immunosuppressive environment
Jiali Qian,
Chuxin Huang,
Mimi Wang,
Ying Liu,
Yingying Zhao,
Miao Li,
Xi Zhang,
Xiangyu Gao,
Yawen Zhang,
Yi Wang,
Jinya Huang,
Jiajun Li,
Qiwen Zhou,
Rui Liu,
Xuanchun Wang,
Jiefeng Cui,
Yehong Yang
Affiliations
Jiali Qian
Department of endocrinology, Huashan Hospital, Fudan University, Shanghai, China
Chuxin Huang
Department of endocrinology, Huashan Hospital, Fudan University, Shanghai, China
Mimi Wang
Liver Cancer Institute, Zhongshan Hospital, Fudan University & Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China
Ying Liu
Department of endocrinology, Huashan Hospital, Fudan University, Shanghai, China
Yingying Zhao
Liver Cancer Institute, Zhongshan Hospital, Fudan University & Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China
Miao Li
Liver Cancer Institute, Zhongshan Hospital, Fudan University & Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China
Xi Zhang
Liver Cancer Institute, Zhongshan Hospital, Fudan University & Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China
Xiangyu Gao
Department of endocrinology, Huashan Hospital, Fudan University, Shanghai, China
Yawen Zhang
Department of endocrinology, Huashan Hospital, Fudan University, Shanghai, China
Yi Wang
Department of endocrinology, Huashan Hospital, Fudan University, Shanghai, China
Jinya Huang
Department of endocrinology, Huashan Hospital, Fudan University, Shanghai, China
Jiajun Li
Liver Cancer Institute, Zhongshan Hospital, Fudan University & Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China
Qiwen Zhou
Liver Cancer Institute, Zhongshan Hospital, Fudan University & Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China
Rui Liu
Department of endocrinology, Huashan Hospital, Fudan University, Shanghai, China
Xuanchun Wang
Department of endocrinology, Huashan Hospital, Fudan University, Shanghai, China
Jiefeng Cui
Liver Cancer Institute, Zhongshan Hospital, Fudan University & Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China; Corresponding author.
Yehong Yang
Department of endocrinology, Huashan Hospital, Fudan University, Shanghai, China; Corresponding author.
Although some cohort studies have indicated a close association between diabetes and HCC, the underlying mechanism about the contribution of diabetes to HCC progression remains largely unknown. In the study, we applied a novel HCC model in SD rat with diabetes and a series of high glucose-stimulated cell experiments to explore the effect of a high glucose environment on HCC metastasis and its relevant mechanism. Our results uncovered a novel regulatory mechanism by which nuclear translocation of metabolic enzyme PKM2 mediated high glucose-promoted HCC metastasis. Specifically, high glucose-increased PKM2 nuclear translocation downregulates chemerin expression through the redox protein TRX1, and then strengthens immunosuppressive environment to promote HCC metastasis. To the best of our knowledge, this is the first report to elucidate the great contribution of a high glucose environment to HCC metastasis from a new perspective of enhancing the immunosuppressive microenvironment. Simultaneously, this work also highlights a previously unidentified non-metabolic role of PKM2 and opens a novel avenue for cross research and intervention for individuals with HCC and comorbid diabetes.
