Disruption of the p53-Notchl pathway in the development of human epithelial cancers

人类细胞已经进化出多种保障机制，以防止细胞异常生长。我们鉴定了新的“P53-Notch1”途径，并指出了它的肿瘤抑制作用。我们揭示了它是如何在癌细胞中被破坏的。特别是，P53家族成员P63被发现通过已确定的P53反应元件直接抑制P53依赖和非依赖的Notch1抑癌基因的诱导，从而维持上皮细胞的增殖能力。

Human cells have evolved multiple safeguard mechanisms to prevent aberrant cell growth. We have identified the novel "p53-Notchl" pathway and pointed out its tumor suppressive role. We revealed how it is disrupted in cancer cells. Particularly, the p53 family member, p63, is found to inhibit both p53-dependent and -independent induction of the Notchl tumor suppressor gene directly through the identified p53-responsive element, thereby maintaining the proliferative capacity of epithelial cells.