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Abstract：
Hyperactivation of Wnt/β-catenin (canonical) signaling in colorectal cancers (CRCs) was identified in the 1990s. Most CRC patients have mutations in genes that encode components of the Wnt pathway. Inactivating mutations in the adenomatous polyposis coli (APC) gene, which encodes a protein necessary for β-catenin degradation, are by far the most prevalent. Other Wnt signaling components are mutated in a smaller proportion of CRCs; these include a FZD-specific ubiquitin E3 ligase known as ring finger protein 43 that removes FZDs from the cell membrane. Our understanding of the genetic and epigenetic landscape of CRC has grown exponentially because of contributions from high-throughput sequencing projects such as The Cancer Genome Atlas. Despite this, no Wnt modulators have been successfully developed for CRC-targeted therapies. In this review, we will focus on the Wnt receptor complex, and speculate on recent discoveries about ring finger protein 43regulating Wnt receptors in CRCs. We then review the current debate on a new APC-Wnt receptor interaction model with therapeutic implications.
摘要：
在1990年代发现了结直肠癌（CRC）中Wnt/β-catenin（规范）信号的过度激活。大多数CRC患者在编码Wnt途径组分的基因中具有突变。腺瘤性结肠息肉病（APC）基因的失活突变，它编码β-连环蛋白降解所必需的蛋白质，是迄今为止最普遍的。其他Wnt信号传导成分在较小比例的CRC中突变;这些包括称为环指蛋白43的FZD特异性泛素E3连接酶,其从细胞膜去除FZD。由于高通量测序项目（如癌症基因组图谱）的贡献，我们对CRC的遗传和表观遗传景观的理解呈指数级增长。尽管如此,尚未成功开发用于CRC靶向治疗的Wnt调节剂。在这次审查中,我们将专注于Wnt受体复合物，并推测有关环指蛋白43调节CRC中Wnt受体的最新发现。然后，我们回顾了当前关于具有治疗意义的新型APC-Wnt受体相互作用模型的辩论。
