Abstract
Signaling from the epidermal growth factor receptor (EGFR) elicits multiple biological responses, including cell proliferation, migration, and survival. Receptor endocytosis and trafficking are critical physiological processes that control the strength, duration, diversification, and spatial restriction of EGFR signaling through multiple mechanisms, which we review in this chapter. These mechanisms include: (i) regulation of receptor density and activation at the cell surface; (ii) concentration of receptors into distinct nascent endocytic structures; (iii) commitment of the receptor to different endocytic routes; (iv) endosomal sorting and postendocytic trafficking of the receptor through distinct pathways, and (v) recycling to restricted regions of the cell surface. We also highlight how communication between organelles controls EGFR activity along the endocytic route. Finally, we illustrate how abnormal trafficking of EGFR oncogenic mutants, as well as alterations of the endocytic machinery, contributes to aberrant EGFR signaling in cancer.
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Acknowledgements
We thank Rosalind Gunby for critically reading the manuscript. This work was supported by grants from the Associazione Italiana per la Ricerca sul Cancro to PPDF (IG 14404 and MCO 10.000); MIUR (the Italian Ministry of University and Scientific Research), the Italian Ministry of Health, and The Monzino Foundation to PPDF; and the WWCR (Worldwide Cancer Research) to SS (16-1245).
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Caldieri, G., Malabarba, M.G., Di Fiore, P.P., Sigismund, S. (2018). EGFR Trafficking in Physiology and Cancer. In: Lamaze, C., Prior, I. (eds) Endocytosis and Signaling. Progress in Molecular and Subcellular Biology, vol 57. Springer, Cham. https://doi.org/10.1007/978-3-319-96704-2_9
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