Research Paper Volume 13, Issue 18 pp 22208—22231
Involvement of c-Myc in low dose radiation-induced senescence enhanced migration and invasion of unirradiated cancer cells
- 1 Department of Radiation Oncology, Taipei City Hospital, Taipei 110, Taiwan
- 2 Radiotherapy, Department of Medical Imaging, Cheng Hsin General Hospital, Taipei 112, Taiwan
- 3 Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
- 4 Cancer Progression Research Center, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
- 5 Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, NJ 08903-2681, USA
- 6 Institute of Neuroscience, National Cheng Chi University, Taipei 116, Taiwan
Received: February 4, 2021 Accepted: August 11, 2021 Published: September 22, 2021https://doi.org/10.18632/aging.203527
How to Cite
Copyright: © 2021 Leu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Ionizing radiation is known to cause cell apoptosis at high dose range, but little is known about the cellular response to low dose radiation. In this study, we found that conditioned medium harvested from WI-38 lung fibroblasts and H1299 lung adenocarcinoma cells exposed to 0.1Gy to 1Gy could enhance the migration and invasion of unirradiated H1299 cells in both 2D and 3D culturing circumstances. Low dose radiation did not induce apoptosis, but induced senescence in irradiated cells. We next examined the expression of immediately early genes including c-Myc and K-Ras. Although both genes could be up-regulated by low dose radiation, induction of c-Myc was more specific to low dose range (0.5Gy) at transcriptional and translational levels. Knockdown of c-Myc by shRNA could repress the senescence induced by low dose radiation. The conditioned medium of irradiated cells induced migration of unirradiated cells was also repressed by knockdown of c-Myc. The c-Myc inhibitor 10058-F4 could suppress low dose radiation induced cell senescence, and the conditioned medium harvested from irradiated cells pretreated with 10058-F4 also lost the ability to enhance the migration of unirradiated cells. The cytokine array analysis revealed that immunosuppressive monocyte chemoattractant protein-1 increased by low dose radiation could be repressed by 10058-F4. We also showed that 10058-F4 could suppress low dose radiation induced tumor progression in a xenograft tumor model. Taken together, current data suggest that -Myc is involved in low dose radiation induced cell senescence and potent bystander effect to increase the motility of unirradiated cells.