细胞与邻近细胞的粘附是多细胞生物体中组织形态发生所需的基本生物学过程。细胞-细胞粘附之间的紧密协调,信令,基因表达是正常组织的特征。Changes,这种协调经常中断,在侵袭性和转移性癌症发展过程中很常见。Wnt/β-catenin信号通路是研究粘附介导的信号通路在结直肠癌(CRC)侵袭和转移中的作用的良好模型。因为β-连环蛋白在细胞中具有双重作用;它是钙黏着蛋白跨膜受体与细胞骨架的主要粘附接头,此外,它也是Wnt信号传导到细胞核的关键传感器,它充当Wnt靶基因的共转录激活因子。Wnt/β-连环蛋白信号的过度激活是大多数CRC患者的共同特征。我们发现神经细胞粘附受体L1CAM(L1)是β-catenin信号的靶基因,在CRC患者的癌细胞中被诱导,在CRC转移中起重要作用。在这次审查中,我们将讨论在CRC发展过程中激活的β-catenin靶基因的研究(特别是,L1),受L1影响的信号通路,以及L1过表达激活的下游靶基因的作用,尤其是那些也是肠干细胞基因签名的一部分。由于肠干细胞受Wnt信号高度调节,并且被认为在CRC进展中也起着重要作用,解开这些基因调控的潜在机制将阐明正常的肠道稳态以及侵袭性和转移性CRC的发展。
Cell adhesion to neighboring cells is a fundamental biological process in multicellular organisms that is required for tissue morphogenesis. A tight coordination between cell-cell adhesion, signaling, and gene expression is a characteristic feature of normal tissues. Changes, and often disruption of this coordination, are common during invasive and metastatic cancer development. The Wnt/β-catenin signaling pathway is an excellent model for studying the role of adhesion-mediated signaling in colorectal cancer (CRC) invasion and metastasis, because β-catenin has a dual role in the cell; it is a major adhesion linker of cadherin transmembrane receptors to the cytoskeleton and, in addition, it is also a key transducer of Wnt signaling to the nucleus, where it acts as a co-transcriptional activator of Wnt target genes. Hyperactivation of Wnt/β-catenin signaling is a common feature in the majority of CRC patients. We found that the neural cell adhesion receptor L1CAM (L1) is a target gene of β-catenin signaling and is induced in carcinoma cells of CRC patients, where it plays an important role in CRC metastasis. In this review, we will discuss studies on β-catenin target genes activated during CRC development (in particular, L1), the signaling pathways affected by L1, and the role of downstream target genes activated by L1 overexpression, especially those that are also part of the intestinal stem cell gene signature. As intestinal stem cells are highly regulated by Wnt signaling and are believed to also play major roles in CRC progression, unravelling the mechanisms underlying the regulation of these genes will shed light on both normal intestinal homeostasis and the development of invasive and metastatic CRC.