J Cancer 2017; 8(8):1400-1409. doi:10.7150/jca.18170
Downregulation of Mitochondrial Single Stranded DNA Binding Protein (SSBP1) Induces Mitochondrial Dysfunction and Increases the Radiosensitivity in Non-Small Cell Lung Cancer Cells
1. Hubei Key Laboratory of Tumor Biological Behavior, Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan, China;
2. Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China;
3. Department of Radiation Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
* These authors contributed equally to this work.
Wang Y, Hu L, Zhang X, Zhao H, Xu H, Wei Y, Jiang H, Xie C, Zhou Y, Zhou F. Downregulation of Mitochondrial Single Stranded DNA Binding Protein (SSBP1) Induces Mitochondrial Dysfunction and Increases the Radiosensitivity in Non-Small Cell Lung Cancer Cells. J Cancer 2017; 8(8):1400-1409. doi:10.7150/jca.18170. Available from http://www.jcancer.org/v08p1400.htm
Radiotherapy is one of the major therapeutic strategies for human non-small cell lung cancer (NSCLC), but intrinsic radioresistance of cancer cells makes a further improvement of radiotherapy for NSCLC challenging. Mitochondrial function is frequently dysregulated in cancer cells for adaptation to the changes of tumor microenvironment after exposure to radiation. Therefore, targeting mitochondrial biogenesis and bioenergetics is an attractive strategy to sensitize cancer cells to radiation therapy. In this study, we found that downregulation of single-strand DNA-binding protein 1 (SSBP1) in H1299 cells was associated with inducing mitochondrial dysfunction and increasing radiosensitivity to ionizing radiation. Mechanistically, SSBP1 loss induced mitochondrial dysfunction via decreasing mitochondrial DNA copy number and ATP generation, enhancing the mitochondrial-derived ROS accumulation and downregulating key glycolytic enzymes expression. SSBP1 knockdown increased the radiosensitivity of H1299 cells by inducing increased apoptosis, prolonged G2/M phase arrest and defective homologous recombination repair of DNA double-strand breaks. Our findings identified SSBP1 as a radioresistance-related protein, providing potential novel mitochondrial target for sensitizing NSCLC to radiotherapy.
Keywords: SSBP1, NSCLC, radiosensitivity