Fgl-1 promotes the progression of endometrial adenocarcinoma through PI3K/AKT signal pathway.
Fgl-1 is overexpressed in endometrial adenocarcinoma and its suppression reduces tumor cell viability and migration, suggesting a potential target for future therapies.
Where it sits
this study against the rest of the fgl (fg loop peptide) corpusSummary and findings
This study assessed the role of Fgl-1 expression in endometrial adenocarcinoma (EAC) tissues and cell lines. Fgl-1 was found to be overexpressed in EAC tissues compared to normal endometrium, with a significant correlation to tumor grade. Suppression of Fgl-1 led to a 60% reduction in expression and decreased cell viability, proliferation, migration, and invasion.
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.
Background
Endometrial adenocarcinoma (EAC) is a common malignancy in the female reproductive system. Previous research has indicated that Fibrinogen-like protein 1 (Fgl-1) may play a role in immunosuppression by interacting with lymphocyte activation gene 3 (Lag-3). However, the specific role of Fgl-1 in EAC and its potential as a therapeutic target remain inadequately explored, making this study significant in expanding the understanding of EAC pathology.
Methods
The study employed immunohistochemistry to assess Fgl-1 expression in EAC tissues and normal endometrium. Various assays, including CCK-8 tests, cell clone generation, wound healing, and migration and invasion assays, were used to evaluate the effects of Fgl-1 on cell viability and behavior. Western blotting was utilized to investigate the expression of proteins related to epithelial-mesenchymal transition (EMT) and associated signaling pathways.
Results
Fgl-1 was significantly overexpressed in EAC tissues compared to normal endometrium (P<0.01). The expression of Fgl-1 was positively correlated with tumor grade (P=0.011). Knockdown of Fgl-1 led to a 60% reduction in its expression, which was associated with decreased cell viability, proliferation, migration, and invasion. Additionally, Fgl-1 suppression inhibited PI3K/AKT signaling in KLE cells.
Interpretation
The findings suggest that Fgl-1 acts as an oncogenic driver in EAC by activating the PI3K/AKT signaling pathway, which is consistent with its role in promoting EMT. While the statistical significance of the results is clear, the clinical relevance of targeting Fgl-1 in EAC requires further validation through human studies. Limitations include the reliance on in vitro models and the absence of clinical trial data.
Key findings
- Fgl-1 was markedly overexpressed in EAC tissues compared with normal endometrium (P<0.01).
- Fgl-1 expression was positively correlated to tumor grade (P=0.011).
- Lentiviral silencing reduced Fgl-1 expression by 60%.
- Fgl-1 suppression inhibited PI3K/AKT signaling in KLE cells.
Limitations
- Primarily in vitro study.
- No human clinical trial data reported.
- Small sample size in tissue analysis.
- Potential confounding factors not controlled.