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 language | English (US) |
---|---|
Title of host publication | Vesicle Trafficking in Cancer |
Publisher | Springer New York |
Pages | 303-325 |
Number of pages | 23 |
Volume | 9781461465287 |
ISBN (Electronic) | 9781461465287 |
ISBN (Print) | 1461465273, 9781461465270 |
DOIs | |
State | Published - Jul 1 2013 |
ASJC Scopus subject areas
- Medicine(all)