Medical Research Council, Toxicology Unit, Hodgkin Building, Leicester University, Leicester, UK.
Cell Death Differ. 2011 Sep;18(9):1487-99. doi: 10.1038/cdd.2011.81. Epub 2011 Jul 15.
p53 mutations, occurring in two-thirds of all human cancers, confer a gain of function phenotype, including the ability to form metastasis, the determining feature in the prognosis of most human cancer. This effect seems mediated at least partially by its ability to physically interact with p63, thus affecting a cell invasion pathway, and accordingly, p63 is deregulated in human cancers. In addition, p63, as an 'epithelial organizer', directly impinges on epidermal mesenchimal transition, stemness, senescence, cell death and cell cycle arrest, all determinant in cancer, and thus p63 affects chemosensitivity and chemoresistance. This demonstrates an important role for p63 in cancer development and its progression, and the aim of this review is to set this new evidence that links p63 to metastasis within the context of the long conserved other functions of p63.
p53 突变发生在三分之二的所有人类癌症中,赋予了功能获得表型,包括形成转移的能力,这是大多数人类癌症预后的决定性特征。这种效应似乎至少部分是通过其与 p63 物理相互作用的能力介导的,从而影响细胞侵袭途径,因此 p63 在人类癌症中失调。此外,p63 作为“上皮组织者”,直接影响表皮间充质转化、干性、衰老、细胞死亡和细胞周期停滞,这些都是癌症的决定因素,因此 p63 影响化疗敏感性和化疗耐药性。这表明 p63 在癌症的发展和进展中起着重要作用,本综述的目的是在 p63 的其他长期保守功能的背景下,将这一新的证据与 p63 与转移联系起来。