Frontiers in Cell and Developmental Biology (Jul 2021)
JFK Is a Hypoxia-Inducible Gene That Functions to Promote Breast Carcinogenesis
- Ziran Yang,
- Xuehong Zhou,
- Enrun Zheng,
- Yizhou Wang,
- Xinhua Liu,
- Yue Wang,
- Yue Wang,
- Yanpu Wang,
- Zhaofei Liu,
- Fei Pei,
- Yue Zhang,
- Jie Ren,
- Yunchao Huang,
- Lu Xia,
- Sudun Guan,
- Sen Qin,
- Feiya Suo,
- Jie Shi,
- Lijing Wang,
- Lin He,
- Lin He,
- Luyang Sun,
- Luyang Sun
Affiliations
- Ziran Yang
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Health Science Center, Beijing, China
- Xuehong Zhou
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Health Science Center, Beijing, China
- Enrun Zheng
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Health Science Center, Beijing, China
- Yizhou Wang
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Health Science Center, Beijing, China
- Xinhua Liu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou, China
- Yue Wang
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Health Science Center, Beijing, China
- Yue Wang
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou, China
- Yanpu Wang
- Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
- Zhaofei Liu
- Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
- Fei Pei
- Department of Pathology, Peking University Third Hospital, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
- Yue Zhang
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Health Science Center, Beijing, China
- Jie Ren
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Health Science Center, Beijing, China
- Yunchao Huang
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Health Science Center, Beijing, China
- Lu Xia
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Health Science Center, Beijing, China
- Sudun Guan
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Health Science Center, Beijing, China
- Sen Qin
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Health Science Center, Beijing, China
- Feiya Suo
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Health Science Center, Beijing, China
- Jie Shi
- National Institute on Drug Dependence, Peking University, Beijing, China
- Lijing Wang
- Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou, China
- Lin He
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Health Science Center, Beijing, China
- Lin He
- National Institute on Drug Dependence, Peking University, Beijing, China
- Luyang Sun
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Health Science Center, Beijing, China
- Luyang Sun
- Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
- DOI
- https://doi.org/10.3389/fcell.2021.686737
- Journal volume & issue
-
Vol. 9
Abstract
Many carcinomas feature hypoxia, a condition has long been associated with tumor progression and poor prognosis, as well as resistance to chemoradiotherapy. Here, we report that the F-box protein JFK promotes mammary tumor initiation and progression in MMTV-PyMT murine model of spontaneous breast cancer. We find that JFK is inducible under hypoxic conditions, in which hypoxia-inducible factor HIF-1α binds to and transcriptionally activates JFK in breast cancer cells. Consistently, analysis of public clinical datasets reveals that the mRNA level of JFK is positively correlated with that of HIF-1α in breast cancer. We show that JFK deficiency leads to a decrease in HIF-1α-induced glycolysis in breast cancer and sensitizes hypoxic breast cancer cells to ionizing radiation and chemotherapeutic treatment. These results indicate that JFK is an important player in hypoxic response, supporting the pursuit of JFK as a potential therapeutic target for breast cancer intervention.
Keywords
