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护机制来防止异常细胞生长。我们已经鉴定了新的“p53-Notchl”通路，并指出其肿瘤抑制作用。我们揭示了它是如何在癌细胞中被破坏的。特别地，发现p53家族成员p63直接通过鉴定的p53响应元件抑制Notchl肿瘤抑制基因的p53依赖性和非依赖性诱导，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.