Department of Pathology, Josephine Nefkens Institute, Erasmus MC, Rotterdam, The Netherlands.
J Pathol. 2010 Jul;221(3):239-41. doi: 10.1002/path.2718.
Inactivation of the APC tumour suppressor gene represents the rate-limiting event in colorectal cancer. Loss of APC function leads to constitutive activation of the canonical Wnt-beta-catenin signalling pathway, thus resulting into a broad spectrum of cellular defects, ranging from stem cell self-renewal and differentiation, apoptosis, migration and proliferation. Recently, Phelps et al presented an alternative model where loss of APC does not primarily result in Wnt signalling activation but rather involves the transcriptional co-repressor CtBP1. According to this alternative scenario, oncogenic KRAS activation represents a conditio sine qua non for nuclear beta-catenin translocation and Wnt activation. In a recent issue of the Journal of Pathology, Obrador-Hevia and collaborators reaffirmed the broadly accepted textbook model by showing the presence of nuclear beta-catenin in both the presence and, more often, the absence of KRAS mutations.
APC 肿瘤抑制基因失活是结直肠癌的限速事件。APC 功能丧失导致经典 Wnt-β-连环蛋白信号通路的组成性激活，从而导致广泛的细胞缺陷，从干细胞自我更新和分化、凋亡、迁移和增殖。最近，Phelps 等人提出了一种替代模型，其中 APC 的丢失并不主要导致 Wnt 信号激活，而是涉及转录共抑制因子 CtBP1。根据这种替代方案，致癌性 KRAS 激活是核β-连环蛋白易位和 Wnt 激活的必要条件。在《病理学杂志》的最近一期中，Obrador-Hevia 及其合作者通过显示核β-连环蛋白在 KRAS 突变存在和更常见的缺失时都存在，从而再次证实了广泛接受的教科书模型。
