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.
Department of General Surgery, The Second People's Hospital of Jingmen, Jingmen, 448000, China.
Cell Mol Life Sci. 2018 Mar;75(6):965-973. doi: 10.1007/s00018-017-2666-y. Epub 2017 Oct 3.
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.
作为肿瘤抑制因子 p53 家族的一员，p63 是一种编码多功能蛋白变体的基因，它与癌症的发生和发展相关，尽管在癌症患者中很少发生突变。然而，p63 是癌基因还是肿瘤抑制基因一直存在争议。在这里，我们全面回顾了 p63 在发育、肿瘤发生和肿瘤进展中的作用。根据分子细胞生物学、遗传模型和临床研究的数据，我们得出结论，p63 在不同的情况下可能作为癌基因或肿瘤抑制基因发挥作用：p63 基因的 TA 异构体通常通过抑制细胞增殖、存活和转移来发挥肿瘤抑制作用；然而，ΔN 异构体可能通过促进细胞增殖和存活引发肿瘤发生，但抑制肿瘤转移和进展；p63 对肿瘤形成和进展的影响取决于整个 p53 家族的背景，p63 基因座的扩增或缺失都可能打破平衡导致肿瘤发生。
