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Mitochondrial KATP Channels Control Glioma Radioresistance by Regulating ROS-Induced ERK Activation

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Abstract

Malignant glioma is the most prevalent form of malignant brain tumor. Although radiotherapy is widely used in glioma treatment, the radioresistance of glioma cells limits the success of the glioma treatment. The lack of effective targets and signaling pathways to reverse glioma radioresistance is the critical obstacle in successful treatment. In this study, we demonstrate that mitochondrial ATP-sensitive potassium channels (mtKATP channels) are overexpressed in glioma cells and are closely related to the malignancy grade and the overall survival of the patients. Importantly, we showed that mtKATP channels could control glioma radioresistance by regulating reactive oxygen species (ROS)-induced ERK activation. The inhibition of mtKATP channels suppresses glioma radioresistance by inhibiting ERK activation both in vitro and in vivo. These findings reveal the important roles of the mitochondria and mtKATP channels as key regulators in the radioresistance of glioma cells, and suggest that mtKATP channel blockers and MAPK/ERK kinase (MEK) inhibitors are potential targets for drug development of glioma treatments.

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Acknowledgments

The authors acknowledge the National Natural Science Foundation of China (81001129 to L.H., 30900581 to B.L., 30971183 and 81041068 to H.G., 30971193 and 81272180 to F.Z.), National Basic Research Program of China, (2012CB518200 to F.Z.), Guangdong Natural Science Foundation (10451051501004726 to L.H.), Medical Scientific Research Foundation of Guangdong Province (B2010170 to L.H.), Guangdong Provincial Science and Technology Program (2009B03080123 to H.G.), Foundation for Distinguished Young Talents in Higher Education of Guangdong (LYM10049 to L.H.), and Foundation of President of School of Public Health and Tropical Medicine in Southern Medical University (GW200807 to L.H.).

Conflict of Interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou, 510515, Guangdong, China

    Lianyan Huang, Shihao Tang, Wenjun Li & Fei Zou

  2. Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China

    Boxing Li

  3. Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China

    Hongbo Guo

  4. Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, China

    Wenjuan Yan

  5. The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China

    Xiaozhou Huang

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  1. Lianyan Huang
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  5. Wenjun Li
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  6. Xiaozhou Huang
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Correspondence to Fei Zou.

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Lianyan Huang and Boxing Li contributed equally to this work.

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Huang, L., Li, B., Tang, S. et al. Mitochondrial KATP Channels Control Glioma Radioresistance by Regulating ROS-Induced ERK Activation. Mol Neurobiol 52, 626–637 (2015). https://doi.org/10.1007/s12035-014-8888-1

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  • DOI: https://doi.org/10.1007/s12035-014-8888-1

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