Malignant conversion of epithelial cancers through dysregulation of the p63-MYC pathway

癌细胞是通过多种基因改变从正常细胞进化而来的。特别是，确定获得转移能力的遗传原因对于阐明癌症的性质非常重要。在本研究中，我发现p63作为上皮发育和干细胞维持的主要调节因子，在癌变早期通过增加细胞的增殖能力同时抑制转移性肿瘤的进展，作为癌基因和肿瘤抑制因子的可能性。我首次提出，c-MYC癌基因的上调消除了p63缺失引起的增生性缺陷，从而在上皮癌发展的晚期引发恶性转化。

Cancer cells evolve from normal cells through multiple genetic alterations. In particular, identification of a genetic cause behind the acquisition of the metastatic ability is very important for elucidating the nature of cancer.In this study, I have found the possibility that p63, master regulator of epithelial development and stemness maintenance, acts as both an oncogene and tumor suppressor by increasing the proliferative capacity of cells while constraining metastatic tumor progression in early stages of carcinogenesis. I propose, for the first time, that up-regulation of c-MYC oncogene cancels the proliferative defect induced by p63 loss, thereby triggering malignant conversion in late stages of epithelial cancer development.