Fgl-1 promotes the progression of endometrial adenocarcinoma through PI3K/AKT signal pathway.

Abstract

Endometrial adenocarcinoma (EAC) represents a prevalent malignancy of the female reproductive tract. Fibrinogen-like protein 1 (Fgl-1), an emerging immune checkpoint ligand expressed by tumor cells, mediates immunosuppression by binding to lymphocyte activation gene 3 (Lag-3). However, the clinicopathological significance and oncogenic role of Fgl-1 in EAC remain poorly understood. This study aimed to assess the role of Fgl-1 expression in EAC using immunohistochemistry. The effects of Fgl-1 on viability, migration, and invasion were assessed using the CCK-8 test, cell clone generation, wound healing, and cell migration and invasion assays. A Western blot was used to determine how Fgl-1 affects the outcome of epithelial-mesenchymal transition (EMT)-associated proteins and to investigate the expression of proteins involved in related signaling pathways. Fgl-1 was markedly overexpressed in EAC tissues compared with normal endometrium (P<0.01), with expression positively correlated to tumor grade (P=0.011). Western blotting confirmed high Fgl-1 levels in EAC cell lines, particularly HEC1B and KLE, which were used for knockdown experiments. Lentiviral silencing reduced Fgl-1 expression by 60%, leading to decreased cell viability, proliferation, migration, and invasion. Furthermore, Fgl-1 suppression inhibited PI3K/AKT signaling in KLE cells, suggesting its oncogenic role via EMT regulation and pathway activation. Together, these findings demonstrate that Fgl-1 acts as an oncogenic driver in EAC by activating PI3K/AKT signaling to promote tumor progression and EMT, suggesting that targeting the Fgl-1 pathway represents a promising therapeutic strategy for EAC immunotherapy.