通过卷曲受体和上皮-间质转化进行癌症化学预防。

Cancer chemoprevention through Frizzled receptors and EMT.

作者信息

Sompel K, Elango A, Smith A J, Tennis M A

机构信息

Division of Pulmonary Sciences and Critical Care Medicine, School of Medicine, University of Colorado Anschutz Medical Campus, 12700 E 19th AVE, RC2 Box C272, Aurora, CO 80045 USA.

出版信息

Discov Oncol. 2021;12(1):32. doi: 10.1007/s12672-021-00429-2. Epub 2021 Sep 9.

Abstract

Frizzled (FZD) transmembrane receptors are well known for their role in β-catenin signaling and development and now understanding of their role in the context of cancer is growing. FZDs are often associated with the process of epithelial to mesenchymal transition (EMT) through β-catenin, but some also influence EMT through non-canonical pathways. With ten different FZDs, there is a wide range of activity from oncogenic to tumor suppressive depending on the tissue context. Alterations in FZD signaling can occur during development of premalignant lesions, supporting their potential as targets of chemoprevention agents. Agonizing or antagonizing FZD activity may affect EMT, which is a key process in lesion progression often targeted by chemoprevention agents. Recent studies identified a specific FZD as important for activity of an EMT inhibiting chemopreventive agent and other studies have highlighted the previously unrecognized potential for targeting small molecules to FZD receptors. This work demonstrates the value of investigating FZDs in chemoprevention and here we provide a review of FZDs in cancer EMT and their potential as chemoprevention targets.

摘要

卷曲蛋白(FZD)跨膜受体因其在β-连环蛋白信号传导和发育中的作用而广为人知,目前人们对其在癌症背景下的作用的认识也在不断加深。FZD通常通过β-连环蛋白与上皮-间质转化(EMT)过程相关,但也有一些通过非经典途径影响EMT。FZD有十种不同类型,根据组织背景,其活性范围从致癌到抑癌广泛存在。在癌前病变发展过程中可能会发生FZD信号改变,这支持了它们作为化学预防剂靶点的潜力。激动或拮抗FZD活性可能会影响EMT,而EMT是病变进展中的一个关键过程,常常是化学预防剂的作用靶点。最近的研究确定了一种特定的FZD对一种抑制EMT的化学预防剂的活性很重要,其他研究也强调了靶向FZD受体的小分子此前未被认识到的潜力。这项工作证明了在化学预防中研究FZD的价值,在此我们对FZD在癌症EMT中的作用及其作为化学预防靶点的潜力进行综述。

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