Recent advances in the study of FAT family genes in lung cancer.

Abstract

The FAT atypical cadherin (FAT) gene family comprises FAT atypical cadherin 1 (FAT1), 2 (FAT2), 3 (FAT3), and 4 (FAT4). These transmembrane adhesion proteins are essential for regulating cell polarity, adhesion, and migration, and are involved in multiple signaling transduction pathways. With the advancement of tumor genomics research, the mutation, expression, and functional regulation of FAT in various cancer types have been elucidated, particularly in non-small cell lung cancer, where FAT has significant biological implications and promising clinical applications. FAT1, a frequently mutated member of the family, participates in remodeling the immune microenvironment via the Wnt/β-catenin, Hippo, and transforming growth factor-beta (TGF-β) pathways. It also influences immune cell infiltration, immune checkpoint expression, and tumor mutational burden, thereby affecting the efficacy of immunotherapy. FAT2 influences cell migration and immune response by modulating cytoskeletal dynamics and the expression of immunochemokines. The non-coding RNA circular RNA FAT3 (circFAT3) may contribute to tumor growth and metastasis. FAT4, a major upstream regulator of the Hippo signaling pathway, inhibits Yes-associated protein/transcriptional coactivator with PDZ-binding motif, maintains cell polarity, and plays multiple roles by regulating the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/ protein kinase B (AKT) pathways and promoting anti-immune escape. This study comprehensively integrated and analyzed research results on the characteristics of the FAT gene family in lung cancer, focusing on its mutations, signaling pathways, and immunological roles, as well as its clinical significance in terms of prognosis. This study provides theoretical support and references for the development of targeted therapeutic strategies.