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A functional interplay between Δ133p53 and ΔNp63 in promoting glycolytic metabolism to fuel cancer cell proliferation

Oncogene volume 37, pages 2150–2164 (2018)Cite this article

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Abstract

Although ΔNp63 is known to promote cancer cell proliferation, the underlying mechanism behind its oncogenic function remains elusive. We report here a functional interplay between ΔNp63 and Δ133p53. These two proteins are co-overexpressed in a subset of human cancers and cooperate to promote cell proliferation. Mechanistically, Δ133p53 binds to ΔNp63 and utilizes its transactivation domain to upregulate GLUT1, GLUT4, and PGM expression driving glycolysis. While increased glycolysis provides cancer cells with anabolic metabolism critical for proliferation and survival, it can be harnessed for selective cancer cell killing. Indeed, we show that tumors overexpressing both ΔNp63 and Δ133p53 exhibit heightened sensitivity to vitamin C that accumulate to a lethal level due to accelerated uptake via overexpressed GLUT1. These observations offer a new therapeutic avenue that could be exploited for clinical applications.

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Acknowledgements

This work was supported in part by the Morningside Foundation, the Zhu Fund and grants from the National Cancer Institute at the National Institute of Health (R01CA85679, R01CA167814, and R01CA125144).

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Author notes

  1. Lu Gong and Xiao Pan are co-first authors contributed equally to this work.

Authors and Affiliations

  1. Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA

    Lu Gong, Chuan-Bian Lim, Anna de Polo & Zhi-Min Yuan

  2. John B. Little Center for Radiation Sciences, Boston, MA, USA

    Lu Gong, Chuan-Bian Lim, Anna de Polo, John B. Little & Zhi-Min Yuan

  3. First Affiliated Hospital and Institute of Translational Medicine, School of Medicine, Zhejiang University, Hangzhou, China

    Xiao Pan

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  1. Lu Gong
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Correspondence to Zhi-Min Yuan.

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Gong, L., Pan, X., Lim, CB. et al. A functional interplay between Δ133p53 and ΔNp63 in promoting glycolytic metabolism to fuel cancer cell proliferation. Oncogene 37, 2150–2164 (2018). https://doi.org/10.1038/s41388-017-0117-8

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