Kelleher Fergal C, Fennelly David, Rafferty Mairin
Department of Medical Oncology, St. Vincent's University Hospital, Dublin, Ireland.
Acta Oncol. 2006;45(4):375-88. doi: 10.1080/02841860600602946.
Cancer may arise because the developmental programs that create the dramatic alterations in form and structure in embryonic development are potentially corrupted. The cells in our bodies retain memories of these processes and cancer can occur later in life if imperfections occur in the fidelity of these pathways. This article is particularly interested in the phenomenon of epithelial to mesenchymal transition, which occurs in embryogenesis. Also reviewed are the small molecules and pathways that are involved both in homeostasis in adult epithelium and embryogenesis in utero. There are five such pathways in particular selected for review in this article: the Wnt pathway, Hedgehog, Notch, PAR and Bone morphogenetic peptide/TGF beta. These are usually conserved throughout mammalian evolution. Though they have been arbitrarily separated in this article they are not exclusive from one another. Their pathologically altered expression is found especially frequently in childhood tumours where they may recapitulate their developmental role, and in tumours that resemble primitive precursor cells. These pathways are important for selecting cell fates, cellular rearrangements, cytological context and morphologic design in embryology as well as participating in epithelial function in adults.
癌症的发生可能是因为在胚胎发育过程中引起形态和结构发生显著变化的发育程序可能被破坏。我们体内的细胞保留着这些过程的记忆,如果这些途径的保真度出现缺陷,癌症可能在生命后期发生。本文特别关注胚胎发生过程中发生的上皮-间质转化现象。同时也回顾了参与成年上皮细胞稳态和子宫内胚胎发生的小分子和信号通路。本文特别挑选了五条这样的信号通路进行综述:Wnt信号通路、Hedgehog信号通路、Notch信号通路、PAR信号通路和骨形态发生蛋白/TGF-β信号通路。这些信号通路在整个哺乳动物进化过程中通常是保守的。虽然在本文中它们被任意分开,但它们并非相互排斥。它们的病理改变表达尤其常见于儿童肿瘤中,在这些肿瘤中它们可能重现其发育作用,也见于类似于原始前体细胞的肿瘤中。这些信号通路对于胚胎学中选择细胞命运、细胞重排、细胞学背景和形态设计以及参与成年人的上皮功能都很重要。