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ATM pathway is essential for ionizing radiation-induced autophagy
Nan Liang1, Lili Jia, Yang Liu
1Key Laboratory of Radiobiology (Ministry of Health), School of Public Health, Jilin University, Changchun 130021, China.
Cellular Signalling
|September 3, 2013
Summary
Ataxia-telangiectasia mutated (ATM) promotes radiation-induced autophagy in cervical cancer via MAPK14 and mTOR pathways. This ATM-mediated autophagy influences the cells' radiosensitivity.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- The role of Ataxia-telangiectasia mutated (ATM) in DNA damage response is established.
- Its specific function in radiation-induced autophagy within cervical cancer cells remains largely undefined.
Purpose of the Study:
- To elucidate the role of ATM in regulating autophagy in response to ionizing radiation (IR) in cervical cancer.
- To investigate the molecular pathways, including MAPK14, mTOR, and Beclin/PI3KIII complexes, through which ATM influences IR-induced autophagy and radiosensitivity.
Main Methods:
- Establishment of gene-engineered cervical cancer cell lines (Hela) with ATM and MAPK14 knockout.
- Assessment of autophagy using MDC staining and GFP-LC3 relocalization.
- Analysis of protein expression via Western blot and co-immunoprecipitation.
- Evaluation of cell viability (CCK-8) and radiosensitivity (colony formation assays).
Main Results:
- Ionizing radiation (IR) induced autophagy and increased ATM phosphorylation in cervical cancer cells.
- ATM-deficient cells exhibited hypersensitivity to IR but unaffected IR-induced apoptosis.
- ATM inhibition or deficiency significantly reduced IR-induced autophagy, implicating ATM in this process.
- ATM promoted autophagy via the MAPK14 pathway, mTOR signaling, and Beclin/PI3KIII complex formation, impacting radiosensitivity.
Conclusions:
- ATM plays a crucial role in promoting radiation-induced autophagy in cervical cancer cells.
- The mechanism involves the MAPK14 pathway, mTOR signaling, and the Beclin/PI3KIII complex.
- ATM-mediated autophagy significantly contributes to the radiosensitivity of cervical cancer cells.
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