Despite inactivating APC mutations, colorectal cancers express the WNT-effector protein β-catenin in a heterogeneous pattern, with strong nuclear expression confined to a fraction of tumor cells, often only at the tumor's leading edge. WNT-reporter constructs allow separation of these tumor cells with highest WNT/β-Catenin activity, which also express high levels of several putative cancer stem cell antigens. Unexpectedly however, these cells do not show exclusive tumorigenicity in xenograft experiments, thus questioning their general stemness phenotype. Instead, there appears to be significant plasticity between both tumor cells with high and low WNT/β-Catenin activity because both cell types can form tumors which again show mixed populations. Furthermore, WNT/β-Catenin activity in colon cancer cells can be modulated by MAPK signaling thus revealing a means of how other signaling pathways contribute to WNT signaling plasticity in colon cancer.

译文

尽管失活APC突变,大肠癌仍以异质模式表达WNT效应蛋白 β-catenin,其强核表达仅限于一小部分肿瘤细胞,通常仅在肿瘤的前沿。WNT-报告分子构建体允许分离具有最高WNT/β-Catenin活性的这些肿瘤细胞,这些细胞也表达高水平的几种假定的癌症干细胞抗原。然而,出乎意料的是,这些细胞在异种移植实验中没有显示出排他性的致瘤性,因此质疑它们的一般干性表型。相反,两种具有高WNT/β-Catenin活性和低的肿瘤细胞之间似乎都具有显着的可塑性,因为两种细胞类型都可以形成肿瘤,再次显示出混合种群。此外,结肠癌细胞中的WNT/β-Catenin活性可以通过MAPK信号调节,从而揭示了其他信号通路如何促进结肠癌中WNT信号可塑性的手段。

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