방사선의학 웹진

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Abstract

18F-labeled fluorodeoxyglucose (FDG) uptake during FDG positron emission tomography seems to reflect increased radioresistance. However, the exact molecular mechanism underlying high glucose (HG)-induced radioresistance is unclear. In the current study, we showed that ionizing radiation-induced activation of the MEK-ERK-DAPK-p53 signaling axis is required for anoikis (anchorage-dependent apoptosis) of non-small cell lung cancer (NSCLC) cells in normal glucose media. Phosphorylation of DAPK at Ser734 by ERK was essential for p53 transcriptional activity and radiosensitization. In HG media, overexpressed DANGER directly bound to the death domain of DAPK, thus inhibiting the catalytic activity of DAPK. In addition, inhibition of the DAPK-p53 signaling axis by DANGER promoted anoikis-resistance and epithelial-mesenchymal transition (EMT), resulting in radioresistance of HG-treated NSCLC cells. Notably, knockdown of DANGER enhanced anoikis, EMT inhibition, and radiosensitization in a mouse xenograft model of lung cancer. Taken together, our findings offered evidence that overexpression of DANGER and the subsequent inhibitory effect on DAPK kinase activity are critical responses that account for HG-induced radioresistance of NSCLC.

Author information

Kwon T1, Youn H2,3, Son B1, Kim D1, Seong KM4, Park S5, Kim W2,3, Youn B1,2,3.​

1Department of Integrated Biological Science, Pusan National University, Busan, 609-735, Republic of Korea.

2Department of Biological Sciences, Pusan National University, Busan, 609-735, Republic of Korea.

3Nuclear Science Research Institute, Pusan National University, Busan, 609-735, Republic of Korea.

4National Radiation Emergency Medical Center, Korea Institute of Radiological & Medical Sciences, Seoul, 139-706, Republic of Korea.

5Department of Physics, Pusan National University, Busan, 609-735, Republic of Korea.