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Autophagy and its function in radiosensitivity

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Tumor Biology

Abstract

Autophagy differs from apoptosis and is independent of phagocytes by the appearance of autophagosomes, autolysosomes, and complete nuclei in the cell. This process significantly contributes to the antineoplastic effects of radiation. Radiation is an important strategy in cancer treatment; however, many types of cancer show radioresistance. The effects of radiotherapy are affected by factors, including the degree of tumor tissue hypoxia, the ability to repair DNA damage, and the presence of cancer stem cells. We review the relationships among autophagy, the three factors in cancer radiation, and the possible underlying molecular mechanisms. The therapeutic implications of these relationships and mechanisms in clinical settings are also discussed.

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Abbreviations

ULK1:

Unc-51-like autophagy activating kinase 1

mTORC:

Mammalian target of rapamycin

AMPK:

Adenosine monophosphate-activated protein kinase

BECN1:

The class III phosphoinositol-3-kinase Vps34 in a complex with Beclin

LC3:

Light chain 3

HIF-1:

Hypoxia-inducible factor 1

ROS:

Reactive oxygen species

BNIP3:

BCL2 adenovirus E1B 19-kDa interacting protein 3

PI3K:

Phosphoinositide 3 kinase

IR:

Ionizing radiation

DSBs:

DNA double-strand breaks

PERK-ATF4:

Type 1 transmembrane ER-resident protein kinase-activating transcription factor 4

UVRAG:

UV irradiation resistance-associated gene

PARP-1:

Poly(ADP-ribose) polymerase 1

FOXOs:

Forkhead box class O family member proteins

ATM:

Serine/threonine-protein kinase

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Acknowledgments

Our study was supported by the Natural Science Foundation of China (No. 81272504, 81472809), the Innovation Team (No. LJ201123-EH11), Jiangsu Provincial Science and Technology Projects BK2011854 (DA11), and the Six Major Talent Peak Project of Jiangsu Province. The priority academic program development of Jiangsu Higher Education Institution (JX10231801), grants from the Key Academic Discipline of Jiangsu Province “Medical Aspects of Specific Environments,” and “333” Project of Jiangsu Province BRA2012210 (RS12) funded our study.

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    Authors and Affiliations

    1. Department of Radiotherapy, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China

      Yan Yang, Yuehua Yang, Xi Yang, Hongcheng Zhu, Qing Guo, Xiaochen Chen, Hao Zhang & Xinchen Sun

    2. Department of Oncology, People’s Hospital of Taizhou, Taizhou, Jiangsu Province, China

      Qing Guo

    3. Department of Synthetic Internal Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China

      Hongyan Cheng

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    1. Yan Yang
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    2. Yuehua Yang
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    3. Xi Yang
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    4. Hongcheng Zhu
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    5. Qing Guo
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    6. Xiaochen Chen
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    7. Hao Zhang
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    8. Hongyan Cheng
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    9. Xinchen Sun
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    Corresponding author

    Correspondence to Xinchen Sun.

    Additional information

    Yan Yang, Yuehua Yang and Xi Yang contributed equally to this work.

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    Yang, Y., Yang, Y., Yang, X. et al. Autophagy and its function in radiosensitivity. Tumor Biol. 36, 4079–4087 (2015). https://doi.org/10.1007/s13277-015-3496-x

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