Radiation-promoted CDC6 protein stability contributes to radioresistance by regulating senescence and epithelial to mesenchymal transition

Oncogene
Xiaohui YuXiong Li

Abstract

Ionizing radiation (IR) is a conventional cancer therapeutic, to which cancer cells develop radioresistance with exposure. The residual cancer cells after radiation treatment also have increased metastatic potential. The mechanisms by which cancer cells develop radioresistance and gain metastatic potential are still unknown. In this study acute IR exposure induced cancer cell senescence and apoptosis, but after long-term IR exposure, cancer cells exhibited radioresistance. The proliferation of radioresistant cells was retarded, and most cells were arrested in G0/G1 phase. The radioresistant cells simultaneously showed resistance to further IR-induced apoptosis, premature senescence, and epithelial to mesenchymal transformation (EMT). Acute IR exposure steadily elevated CDC6 protein levels due to the attenuation of ubiquitination, while CDC6 overexpression was observed in the radioresistant cells because the insufficiency of CDC6 phosphorylation blocked protein translocation from nucleus to cytoplasm, resulting in subcellular protein accumulation when the cells were arrested in G0/G1 phase. CDC6 ectopic overexpression in CNE2 cells resulted in apoptosis resistance, G0/G1 cell cycle arrest, premature senescence, and EMT, similar ...Continue Reading

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Citations

Jul 15, 2020·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·H ZhaoX Li
Dec 29, 2020·International Journal of Radiation Biology·Zhi Xiong ChongWan Yong Ho
May 1, 2021·Frontiers in Cell and Developmental Biology·Xinyue YuGuanghui Cheng
Mar 29, 2021·Cellular and Molecular Gastroenterology and Hepatology·Jovana R GotovacNicholas J Clemons
Jul 16, 2021·Journal of Radiation Research·Lue SunYuki Sugiura
Aug 31, 2021·Frontiers in Cell and Developmental Biology·Jing YangXing Zhang

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Methods Mentioned

BETA
xenografts
X-ray
flow cytometry
ubiquitination
immunoprecipitation
confocal microscopy
transfection
biopsy
xenograft

Software Mentioned

Graphpad Prism
SPSS

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