Edinburgh Cancer Research

A new role for autophagy in EGFR recycling and signalling

Cancer Research UK Edinburgh Centre scientists demonstrated that autophagy regulates recycling and signalling of Epidermal Growth Factor Receptor: October 2019

The study by Fraser et al. identifies a novel function of the autophagy machinery in recognising damaged early endosomes, the absence of which compromises EGFR trafficking and signalling.
The study by Fraser et al. identifies a novel function of the autophagy machinery in recognising damaged early endosomes, the absence of which compromises EGFR trafficking and signalling.

Endocytosis and autophagy are two cellular processes known to deliver a broad spectrum of cargoes for degradation. Endocytosis involves the invagination (folding inward) of the cell plasma membrane to form endosomes. Growth factor receptors, such as Epidermal Growth Factor Receptor (EGFR), are regulated by endocytosis by fine tuning their availability on the cell surface. Autophagy on the other hand enables orderly degradation and recycling of intracellular components such as damaged organelles. Both processes are crucial for cell homeostasis and share multiple commonalities, but the interplay between autophagy and endocytosis remains relatively unexplored.

In a recent study published in the journal EMBO Reports, researchers from the Cancer Research UK Edinburgh Centre and their collaborators from Babraham Institute in Cambridge demonstrated that the ablation of autophagy-essential players disrupts endocytic trafficking of EGFR upon binding to its ligand, Epidermal Growth Factor (EGF). The work titled “Targeting of early endosomes by autophagy facilitates EGFR recycling and signalling” provided evidence that aberrant early endosomes accumulate in the cells in the absence of autophagy. It also provided important new insights into how this can affect EGFR trafficking and compromise EGF-mediated signalling and survival.  

EGFR signalling is very important for correct development and function of organisms and abnormalities in its activity have been associated with human diseases such as Alzheimer's disease and cancer. Blocking EGFR function can prevent the growth of many tumours improving patients health. Consequently, this study, which was driven by Dr Jane Fraser (as part of her PhD project) and led by Dr Noor Gammoh, may have significant implications for future developments in the field of EGFR-targeted therapeutics.

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