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A double dealing tale of p63: an oncogene or a tumor suppressor

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Abstract

As a member of tumor suppressor p53 family, p63, a gene encoding versatile protein variant, has been documented to correlate with cancer formation and progression, though it is rarely mutated in cancer patients. However, it has long been controversial on whether p63 is an oncogene or a tumor suppressor. Here, we comprehensively reviewed reports on roles of p63 in development, tumorigenesis and tumor progression. According to data from molecular cell biology, genetic models and clinic research, we conclude that p63 may act as either an oncogene or a tumor suppressor gene in different scenarios: TA isoforms of p63 gene are generally tumor-suppressive through repressing cell proliferation, survival and metastasis; ΔN isoforms, however, may initiate tumorigenesis via promoting cell proliferation and survival, but inhibit tumor metastasis and progression; effects of p63 on tumor formation and progression depend on the context of the whole p53 family, and either amplification or loss of p63 gene locus can break the balance to cause tumorigenesis.

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Acknowledgements

This work was supported by National Natural Science Foundation of China (#31671423) and Science and Technology Department of Sichuan Province (#2016JY0152). We thank the members of Zhi-Xiong Xiao lab for stimulative discussions.

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  1. Yonglong Chen and Yougong Peng contributed equally to this work.

Authors and Affiliations

  1. Center of Growth, Metabolism and Aging, Key Laboratory of Biological Resources and Ecological Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, 610065, China

    Yonglong Chen, Shijie Fan, Yimin Li, Zhi-Xiong Xiao & Chenghua Li

  2. Department of General Surgery, The Second People’s Hospital of Jingmen, Jingmen, 448000, China

    Yougong Peng

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  1. Yonglong Chen
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Chen, Y., Peng, Y., Fan, S. et al. A double dealing tale of p63: an oncogene or a tumor suppressor. Cell. Mol. Life Sci. 75, 965–973 (2018). https://doi.org/10.1007/s00018-017-2666-y

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