文章：

肿瘤中WNT通路肿瘤抑制因子的突变和机制

Mutations and mechanisms of WNT pathway tumour suppressors in cancer

原文发布日期：2020-10-23

DOI: 10.1038/s41568-020-00307-z

类型: Review Article

开放获取: 否

英文摘要：

Mutation-induced activation of WNT–β-catenin signalling is a frequent driver event in human cancer. Sustained WNT–β-catenin pathway activation endows cancer cells with sustained self-renewing growth properties and is associated with therapy resistance. In healthy adult stem cells, WNT pathway activity is carefully controlled by core pathway tumour suppressors as well as negative feedback regulators. Gene inactivation experiments in mouse models unequivocally demonstrated the relevance of WNT tumour suppressor loss-of-function mutations for cancer growth. However, in human cancer, a far more complex picture has emerged in which missense or truncating mutations mediate stable expression of mutant proteins, with distinct functional and phenotypic ramifications. Herein, we review recent advances and challenges in our understanding of how different mutational subsets of WNT tumour suppressor genes link to distinct cancer types, clinical outcomes and treatment strategies.

摘要翻译： 

WNT-β-catenin信号通路的突变激活是人类癌症中常见的驱动事件。持续的WNT-β-catenin通路活化赋予癌细胞持续自我更新的生长特性，并与治疗耐药性相关。在健康成体干细胞中，WNT通路活性受到核心通路肿瘤抑制因子及负反馈调节因子的精细调控。小鼠模型中的基因失活实验明确证明了WNT肿瘤抑制因子功能缺失突变对癌症生长的促进作用。然而，在人类癌症中呈现出的图景更为复杂：错义或截短突变介导了突变蛋白的稳定表达，并产生不同的功能和表型影响。本文综述了当前在理解WNT肿瘤抑制基因不同突变亚群如何与特定癌症类型、临床结局及治疗策略相关联方面的研究进展与挑战。

原文链接：

Mutations and mechanisms of WNT pathway tumour suppressors in cancer