title: Stress-Induced EGFR Trafficking: Mechanisms, Functions, and Therapeutic Implications.
abstract: Epidermal growth factor receptor (EGFR) has fundamental roles in normal physiology and cancer, making it a rational target for cancer therapy. Surprisingly, however, inhibitors that target canonical, ligand-stimulated EGFR signaling have proven to be largely ineffective in treating many EGFR-dependent cancers. Recent evidence indicates that both intrinsic and therapy-induced cellular stress triggers robust, noncanonical pathways of ligand-independent EGFR trafficking and signaling, which provides cancer cells with a survival advantage and resistance to therapeutics. Here, we review the mechanistic regulation of noncanonical EGFR trafficking and signaling, and the pathological and therapeutic stresses that activate it. We also discuss the implications of this pathway in clinical treatment of EGFR-overexpressing cancers.
authors.affiliation: Program in Molecular and Cellular Pharmacology, University of Wisconsin-Madison School of Medicine and Public Health, 1300 University Avenue, Madison, WI 53706, USA.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Tan
authors.affiliation: Department of Oncology, University of Wisconsin-Madison School of Medicine and Public Health, 1300 University Avenue, Madison, WI 53706, USA; McArdle Laboratory for Cancer Research, University of Wisconsin-Madison School of Medicine and Public Health, 1300 University Avenue, Madison, WI 53706, USA.
authors.forename: Paul F
authors.initials: PF
authors.lastname: Lambert
authors.affiliation: Department of Human Oncology, University of Wisconsin-Madison School of Medicine and Public Health, 1300 University Avenue, Madison, WI 53706, USA.
authors.forename: Alan C
authors.initials: AC
authors.lastname: Rapraeger
authors.affiliation: Program in Molecular and Cellular Pharmacology, University of Wisconsin-Madison School of Medicine and Public Health, 1300 University Avenue, Madison, WI 53706, USA. Electronic address: raanders@wisc.edu.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Anderson
mesh_terms: D000818:Animals; D001343:Autophagy; D011992:Endosomes / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000378:metabolism* / Q000628:therapy*; D021381:Protein Transport; D013312:Stress, Physiological
chemical_list: D066246:ErbB Receptors
keywords: EGFR; autophagy; cancer therapy; cellular stress; ligand-independent trafficking
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