FLI1 Expression in Invasive Breast Carcinoma: Clinicopathological Correlations and Prognostic Implications

Area of Science:

• Oncology
• Molecular Biology
• Epigenetics

Background:

• The transcription factor Friend Leukemia Integration 1 (FLI1) is implicated in breast cancer aggressiveness, stromal remodeling, and immune modulation.
• Its regulatory mechanisms are poorly understood, though studies link it to the NuRD-LSD1 complex.
• LSD1 inhibition has shown potential in reversing ETS-FLI-driven transcriptional profiles and reducing tumor growth.

Purpose of the Study:

• To evaluate the prognostic significance of FLI1 expression in invasive breast carcinoma (IBC).
• To investigate the association of FLI1 with stromal features in breast cancer.
• To explore FLI1 regulation in response to LSD1 inhibition in preclinical models.

Main Methods:

• Assessed FLI1 expression across multiple IBC patient cohorts.
• Correlated FLI1 levels with histological grade and stromal/immune scores.
• Utilized humanized breast cancer mouse models treated with an LSD1 inhibitor to study FLI1 regulation.

Main Results:

• High FLI1 expression correlated with advanced histological grade in IBC, suggesting an oncogenic role.
• FLI1-high tumors displayed increased stromal and immune scores, indicating involvement in tumor microenvironment remodeling.
• LSD1 inhibition led to downregulation of FLI1 target genes associated with angiogenesis and invasion.

Conclusions:

• FLI1 has a dual role: promoting tumor proliferation and invasion intrinsically, and influencing stromal/endothelial compartments via LSD1-dependent regulation.
• The crosstalk between LSD1 and FLI1 is crucial for immune and stromal remodeling.
• FLI1 serves as a marker of tumor aggressiveness and a potential predictor for response to epigenetic therapies in breast cancer.