An Epitope on EGFR Loading Catastrophic Internalization Serve as a Novel Oncotarget for Hepatocellular Carcinoma...

Area of Science:

• Oncology
• Molecular Biology
• Immunology

Background:

• The role of Epidermal Growth Factor Receptor (EGFR) in Hepatocellular carcinoma (HCC) remains unclear, and current EGFR inhibitors have limited clinical success.
• Targeting rapid EGFR internalization has shown promise in treating EGFR inhibitor-resistant cancers.

Purpose of the Study:

• To evaluate the anti-tumor efficacy of a protein (rLZ-8) from Ganoderma lucidum against HCC.
• To investigate a novel mechanism involving EGFR internalization for HCC therapy.

Main Methods:

• Specific binding of rLZ-8 to EGFR was assessed.
• EGFR internalization, endosomal recycling, and HCC cell death were analyzed.
• A monoclonal antibody with competitive binding to rLZ-8 was screened and characterized.
• An epitope related to EGFR internalization was identified on the extracellular domain.

Main Results:

• rLZ-8 specifically binds to EGFR, enters HCC cells, inhibits endosomal recycling, and induces cell death.
• A screened monoclonal antibody also triggers catastrophic EGFR internalization.
• An internalization-related epitope (S222/K269) on the EGFR extracellular domain was identified.

Conclusions:

• HCC cells exhibit vulnerability to catastrophic EGFR internalization.
• The identified epitope represents a potential therapeutic target for HCC.
• These findings support the development of novel anti-EGFR biologics for HCC treatment.