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Upregulation of the ALDOA/DNA-PK/p53 pathway by dietary restriction suppresses tumor growth

Oncogene volume 37, pages 1041–1048 (2018)Cite this article

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Abstract

Dietary restriction (DR) delays the incidence and decreases the growth of various types of tumors; however, the mechanisms responsible for DR-mediated antitumor effects have not been unequivocally identified. Here, we report that DR suppresses xenograft tumor growth by upregulating a novel signaling pathway. DR led to upregulated aldolase A (ALDOA) expression in xenograft tumors. ALDOA physically interacted with the catalytic subunit of DNA-dependent protein kinase (DNA-PK) and promoted DNA-PK activation. Activated DNA-PK phosphorylated p53 and increased its activity. Although ALDOA can function as an oncogene in cultured cells, it can also activate the tumor suppressor p53. Thus, ALDOA overexpression in the presence of p53 suppressed xenograft tumor growth; however, when p53 was suppressed, ALDOA overexpression promoted xenograft tumor growth. Moreover, we demonstrated that p53 suppression inhibited the antitumor effects of DR. Our results indicate that upregulation of the ALDOA/DNA-PK/p53 pathway is a mechanism accounting for the antitumor effects of DR.

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Acknowledgements

We thank Bin Tan (Chongqing Medical University, Chongqing, China), as well as Guiling Li, Tongke Chen and Yixiang Han (Wenzhou Medical University, Wenzhou, China), for providing technical assistance. This work was supported by the National Natural Science Foundation of China (Grant No. 81572780) and the Zhejiang Provincial Natural Sciences Foundation (Grant No. LZ16H160004).

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Author notes

  1. D Ma, X Chen and P-Y Zhang: These authors contributed equally to this work.

Authors and Affiliations

  1. Digestive Cancer Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China

    D Ma, X Chen, P-Y Zhang, H Zhang, L-J Wei & K-F Tang

  2. Institute of Translational Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China

    D Ma, X Chen, P-Y Zhang, H Zhang, L-J Wei, Y Xu & K-F Tang

  3. Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou, People's Republic of China

    S Hu

  4. Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, People's Republic of China

    J-Z Tang

  5. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China

    M-T Zhou

  6. Department of Radiation Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China

    C Xie

  7. Department of Gynaecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China

    R Ou

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Correspondence to K-F Tang.

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Ma, D., Chen, X., Zhang, PY. et al. Upregulation of the ALDOA/DNA-PK/p53 pathway by dietary restriction suppresses tumor growth. Oncogene 37, 1041–1048 (2018). https://doi.org/10.1038/onc.2017.398

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  • DOI: https://doi.org/10.1038/onc.2017.398

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