Research on the role and mechanism of FAT4 in the development and progression of tumor and non-tumor diseases

FAT4 (FAT Atypical Cadherin 4), a member of the atypical cadherin family, represents the human ortholog of Drosophila Fat (Ft) and functions as a positive regulator of planar cell polarity in the Drosophila wing. It serves various functions during embryogenesis and adult tissue development, demonstrating calcium-dependent adhesive properties. FAT4 has been extensively studied regarding its physiological functions and tumor mechanisms, with numerous studies emphasizing its essential role in various biological processes. A systematic mechanistic analysis and review of its key functions across these various biological processes is lacking. FAT4, as a transmembrane adhesion receptor and tumor suppressor, is expressed in cells across multiple systems, diseases, and diverse cancer tissues. It performs essential functions in diverse biological processes by modulating cell proliferation, polarity, and the immune microenvironment through multiple signaling pathways. This review delineates the functions of FAT4 in tissue morphogenesis, autoimmune diseases, and malignancies. The inactivation of this gene (through mutation, methylation, and deletion) is closely associated with multisystem developmental anomalies, immune responses, and cancer progression, thereby establishing it as a potential prognostic marker and therapeutic target. This study aimed to enhance the understanding of FAT4 and evaluate its potential applications in clinical diagnosis and treatment.