EGFR and Lysosomes: Cell Biology Rewritten by a Single Receptor
An April 2025 study unveils a novel role for the EGFR receptor in lysosomes: it activates mTORC1 without enzymatic function. Here’s why this marks a turning point for science and medicine.
In university classrooms, EGFR is taught as a classic membrane receptor — a key player in cellular communication and tumor proliferation. But according to a study published in Cell Research on April 21, 2025, this view is about to change dramatically. For the first time, researchers have discovered that once EGFR is internalized into lysosomes, it acts entirely independently of its kinase activity, directly activating another powerful metabolic pathway: mTORC1.
A Hidden Function in the Cell’s “Recycling Centers”
Lysosomes — organelles known for waste disposal and molecular recycling — are now the stage for an unprecedented discovery. The study reveals that EGFR is not simply degraded after endocytosis but instead interacts with Rheb, a key activator of mTORC1, functioning as a GEF (guanine nucleotide exchange factor). In essence, it “switches on” Rheb by facilitating the exchange of GDP for GTP, thereby triggering mTORC1 activation.
Without its classical enzymatic activity, EGFR takes on a new role as an alternative — and perhaps even more crucial — metabolic regulator.
Why Is This a Groundbreaking Discovery?
The mTORC1 complex governs cell growth, protein synthesis, autophagy, and energy metabolism. It’s implicated in serious conditions such as:
• Solid tumors
• Metabolic disorders
• Neurodegenerative diseases
Understanding how it’s activated through unexpected pathways — and by familiar actors with novel roles — could:
• Unlock new cancer therapies
• Offer more precise drug targets
• Redefine the very concept of functional segregation in cells
Who Made the Discovery?
The study was conducted by He X., Wang Q.X., and Kang T., and published in the prestigious journal Cell Research, part of the Nature group. The researchers used cutting-edge techniques, including cellular imaging, genetic knockouts, biochemical assays, and proteomic analyses.
(Publication date: April 21, 2025
Official source: Cell Research – Nature)
A New Chapter for Molecular Medicine
The long-held dogma that membrane receptors have a “short life” after endocytosis is now shattered. EGFR proves that even within lysosomes, it can play vital roles, turning what was once thought of as cellular waste into a new therapeutic opportunity.
This discovery opens a promising frontier in the fight against diseases once deemed incurable — bringing science one step closer to true precision medicine.
