Stress-Driven endocytosis of tyrosine-phosphorylated EGFR leads to tumorigenesis: The critical role of oxidative stress

Tzipora Goldkorn, Simone Filosto, Samuel Chung

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Epidermal growth factor receptor (EGFR) dysregulation drives several human pathological conditions, such as glioblastoma and non-small cell lung cancer, and as a result, EGFR activation, internalization, and downregulation are extensively studied for their contributions to tumorigenesis. However, while the mechanisms for ligand-dependent EGFR activation and internalization are quite well understood, current knowledge of ligand-independent mechanisms for EGFR activation and trafficking is obscured by somewhat conflicting data. Thus, unraveling the unorthodox machinery driving stress-induced EGFR activation and trafficking remains a very important task. We present in this chapter the progression of the EGFR field, acknowledging mechanism(s) of stress-dependent activation, internalization, and trafficking of the EGFR. Emphasis is given within the context of cellular oxidative stress, which appears to be a common outcome of several types of stressors and pathological conditions, as observed in cancers and chemotherapy. In addition, c-Cbl, p38 MAPK, c-Src, and caveolin-1 are provided as examples of proteins contributing to the aberrant EGFR internalization and trafficking phenotype observed during cellular stress. Lastly, the role of the membrane itself in stress-induced EGFR internalization is discussed within the context of ceramide, a membrane sphingolipid generated during oxidative stress, and ceramide-enriched lipid rafts.

Original languageEnglish (US)
Title of host publicationVesicle Trafficking in Cancer
PublisherSpringer New York
Pages303-325
Number of pages23
Volume9781461465287
ISBN (Electronic)9781461465287
ISBN (Print)1461465273, 9781461465270
DOIs
StatePublished - Jul 1 2013

ASJC Scopus subject areas

  • Medicine(all)

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    Goldkorn, T., Filosto, S., & Chung, S. (2013). Stress-Driven endocytosis of tyrosine-phosphorylated EGFR leads to tumorigenesis: The critical role of oxidative stress. In Vesicle Trafficking in Cancer (Vol. 9781461465287, pp. 303-325). Springer New York. https://doi.org/10.1007/978-1-4614-6528-7_15