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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
PubMed
Abstract

Insights

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.
Keywords:
ATMAutophagyIonizing radiation

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