<br>HMGB1 蛋白通过阻断有氧呼吸来诱导代谢型肿瘤细胞死亡。,Nature Communications

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HMGB1 蛋白通过阻断有氧呼吸来诱导代谢型肿瘤细胞死亡。
Nature Communications ( IF 14.7 ) Pub Date : 2016-Mar-07 , DOI: 10.1038/ncomms10764
Georg Gdynia _{1,

2} , Sven W Sauer ₃ , Jürgen Kopitz ₁ , Dominik Fuchs ₁ , Katarina Duglova ₁ , Thorsten Ruppert ₃ , Matthias Miller ₄ , Jens Pahl ₄ , Adelheid Cerwenka ₄ , Markus Enders ₅ , Heimo Mairbäurl ₆ , Marcin M Kamiński ₇ , Roland Penzel ₁ , Christine Zhang _{1,

2} , Jonathan C Fuller ₈ , Rebecca C Wade _{8,

9,

10} , Axel Benner ₁₁ , Jenny Chang-Claude _{12,

13} , Hermann Brenner _{14,

15} , Michael Hoffmeister ₁₄ , Hanswalter Zentgraf ₁₆ , Peter Schirmacher _{1,

2,

17} , Wilfried Roth _{1,

2,

17}

Affiliation

Institute of Pathology, Department of Surgical Pathology, University of Heidelberg, 69120 Heidelberg, Germany.
German Cancer Research Center, Clinical Cooperation Unit Molecular Tumor Pathology, 69120 Heidelberg, Germany.
Division of Inborn Metabolic Diseases, Department of General Pediatrics, University Children's Hospital, 69120 Heidelberg, Germany.
German Cancer Research Center, Boveri Junior Research Group Innate Immunity, 69120 Heidelberg, Germany.
Institute of Inorganic Chemistry, Research Group Enders, University of Heidelberg, 69120 Heidelberg, Germany.
Medical Clinic VII, Department of Sports Medicine, University of Heidelberg, and Translational Lung Research Center (TLRC), member of the German Center for Lung Research (DZL), 69120 Heidelberg, Germany.
German Cancer Research Center, Division of Immunogenetics, Tumour Immunology Program, 69120 Heidelberg, Germany.
Molecular and Cellular Modeling Group, Heidelberg Institute for Theoretical Studies (HITS), Department of Molecular and Cellular Modeling (MCM), 69118 Heidelberg, Germany.
Center for Molecular Biology (ZMBH), Molecular and Cellular Modeling (MCM), DKFZ-ZMBH Alliance, Heidelberg University, Heidelberg 69120, Germany.
Interdisciplinary Center for Scientific Computing (IWR), Heidelberg University, 69120 Heidelberg, Germany.
German Cancer Research Center, Division of Biostatistics, 69120 Heidelberg, Germany.
Unit of Genetic Epidemiology, German Cancer Research Center, Division of Cancer Epidemiology, 69120 Heidelberg, Germany.
University Cancer Center Hamburg (UCCH), University Medical Center Hamburg- Eppendorf, 20246 Hamburg, Germany.
German Cancer Research Center (DKFZ), Division of Clinical Epidemiology and Aging Research, 69120 Heidelberg, Germany.
German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Division of Preventive Oncology, 69120 Heidelberg, Germany.
German Cancer Research Center, Division of Monoclonal Antibodies, 69120 Heidelberg, Germany.
Institute of Pathology, Department of Surgical Pathology, University Medical Center Mainz, University of Mainz, 55131 Mainz, Germany.

高迁移率族盒 1 (HMGB1) 蛋白在免疫抗肿瘤防御中发挥核心作用。在这里，我们证明自然杀伤细胞衍生的 HMGB1 通过触发代谢性细胞死亡来直接消除癌细胞。 HMGB1 变构抑制四聚体丙酮酸激酶同工型 M2，从而阻断葡萄糖驱动的有氧呼吸。这导致快速的代谢转变，迫使细胞仅依靠糖酵解来维持能量产生。癌细胞可以通过使用 PKM2 二聚体形式增加糖酵解并利用谷氨酰胺分解来获得对 HMGB1 的抗性。一致地，我们观察到晚期结肠癌中谷氨酰胺分解的关键酶苹果酸酶 1 的表达增加。此外，谷氨酰胺分解的药物抑制使肿瘤细胞对 HMGB1 敏感，为治疗癌症的治疗策略提供了基础。

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更新日期：2016-03-10

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