ILT4 reprograms glucose metabolism to promote tumor progression in triple-negative breast cancer

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• Triple-negative breast cancer (TNBC) is an aggressive subtype with limited treatment options.
• Immunoglobulin-like transcript 4 (ILT4), a myeloid suppressor, is implicated in lung cancer immune evasion.
• The role of ILT4 in breast cancer, particularly TNBC, is largely unknown.

Purpose of the Study:

• To investigate the expression and function of ILT4 in TNBC.
• To elucidate the underlying mechanisms of ILT4-mediated TNBC progression.
• To evaluate ILT4 as a potential therapeutic target for TNBC.

Main Methods:

• Analysis of patient cohort and public databases to assess ILT4 expression in breast cancer subtypes.
• In vitro and in vivo experiments to evaluate the functional role of ILT4 in TNBC cell proliferation, migration, invasion, tumor growth, and metastasis.
• Mechanistic studies involving AKT-mTOR signaling, glucose transporter 3 (GLUT3), and pyruvate kinase muscle 2 (PKM2) to understand ILT4's effects on aerobic glycolysis.

Main Results:

• TNBC exhibits significantly higher ILT4 expression compared to other breast cancer subtypes.
• Enriched ILT4 promotes TNBC cell proliferation, migration, invasion, tumor growth, and metastasis.
• ILT4 upregulates GLUT3 and PKM2 via AKT-mTOR signaling, reprogramming aerobic glycolysis in TNBC cells.
• Inhibition of ILT4 reduces tumor progression and GLUT3/PKM2 expression in vivo.

Conclusions:

• ILT4 is a novel driver of TNBC progression, associated with increased aerobic glycolysis.
• Targeting ILT4 represents a promising therapeutic strategy for combating TNBC.