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 language||English (US)|
|Title of host publication||Vesicle Trafficking in Cancer|
|Publisher||Springer New York|
|Number of pages||23|
|ISBN (Print)||1461465273, 9781461465270|
|State||Published - Jul 1 2013|
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