Matsumoto Shinji, Fujii Shinsuke, Kikuchi Akira
Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan
Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
J Biochem. 2017 Jan;161(1):27-35. doi: 10.1093/jb/mvw069. Epub 2016 Nov 8.
Epithelial tubular morphogenesis (tubulogenesis) is a fundamental morphogenetic process of many epithelial organs. In this developmental process, epithelial cells migrate, proliferate, polarize and differentiate towards surrounding mesenchymal tissue to form tubule structures. Although epithelial tissue structures are basically stable in the postnatal period, epithelial cells regain highly proliferative and invasive potentials within mesenchymal tissue during tumour formation (tumourigenesis). Therefore, there must be a common molecular basis orchestrating the cellular behaviours involved in both tubulogenesis and tumourigenesis. ADP-ribosylation factor (Arf)-like protein 4c (Arl4c), which belongs to the small GTP-binding protein family, is expressed by the simultaneous activation of Wnt-β-catenin and growth factor-Ras-mitogen-activated protein kinase signalling, was identified as an essential regulator of tubulogenesis. Arl4c expression was also involved in the tumour formation of colorectal and lung cancers. In this review, we focus on Arl4c as a novel Wnt signal target molecule that links epithelial tubulogenesis to tumourigenesis.
上皮肾小管形态发生（肾小管形成）是许多上皮器官的基本形态发生过程。在这个发育过程中，上皮细胞向周围间充质组织迁移、增殖、极化并分化，形成管状结构。尽管上皮组织结构在出生后基本稳定，但在肿瘤形成（肿瘤发生）过程中，上皮细胞在间充质组织内重新获得高度增殖和侵袭潜能。因此，必然存在一个共同的分子基础来协调参与肾小管形成和肿瘤发生的细胞行为。ADP核糖基化因子（Arf）样蛋白4c（Arl4c）属于小GTP结合蛋白家族，通过Wnt-β-连环蛋白和生长因子-Ras-丝裂原活化蛋白激酶信号的同时激活而表达，被确定为肾小管形成的关键调节因子。Arl4c的表达也参与了结直肠癌和肺癌的肿瘤形成。在这篇综述中，我们重点关注Arl4c作为一种新的Wnt信号靶分子，它将上皮肾小管形成与肿瘤发生联系起来。
