title: History and progression of Fat cadherins in health and disease.
abstract: Intercellular adhesions are vital hubs for signaling pathways during multicellular development and animal morphogenesis. In eukaryotes, under aberrant intracellular conditions, cadherins are abnormally regulated, which can result in cellular pathologies such as carcinoma, kidney disease, and autoimmune diseases. As a member of the Ca2+-dependent adhesion super-family, Fat proteins were first described in the 1920s as an inheritable lethal mutant phenotype inDrosophila, consisting of four member proteins, FAT1, FAT2, FAT3, and FAT4, all of which are highly conserved in structure. Functionally, FAT1 was found to regulate cell migration and growth control through specific protein-protein interactions of its cytoplasmic tail. FAT2 and FAT3 are relatively less studied and are thought to participate in the development of human cancer through a pathway similar to that of the Ena/VASP proteins. In contrast, FAT4 has been widely studied in the context of biological functions and tumor mechanisms and has been shown to regulate the planar cell polarity pathway, the Hippo signaling pathway, the canonical Wnt signaling cascade, and the expression of YAP1. Overall, Fat cadherins may be useful as emerging disease biomarkers and as novel therapeutic targets.
authors.affiliation: Department of General Surgery; Key Laboratory of Surgery of Zhejiang Province, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary Surgery, Linyi People's Hospital, Linyi, Shandong, People's Republic of China.
authors.forename: Jinghua
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of General Surgery; Key Laboratory of Surgery of Zhejiang Province, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang.
authors.forename: Xiao
authors.initials: X
authors.lastname: Liang
authors.affiliation: Department of General Surgery; Key Laboratory of Surgery of Zhejiang Province, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang.
authors.forename: Jiang
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of General Surgery; Key Laboratory of Surgery of Zhejiang Province, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang.
authors.forename: Junjie
authors.initials: J
authors.lastname: Hong
authors.affiliation: Department of General Surgery.
authors.forename: Libo
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Hepatobiliary Surgery, Linyi People's Hospital, Linyi, Shandong, People's Republic of China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: He
authors.affiliation: Department of General Surgery; Key Laboratory of Surgery of Zhejiang Province, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang.
authors.forename: Xiujun
authors.initials: X
authors.lastname: Cai
keywords: CpG island; FAT1; FAT2; FAT3; FAT4; Fat cadherins; Hippo pathway; WNT signaling