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 |
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ASJC Scopus subject areas
- Medicine(all)
Cite this
Stress-Driven endocytosis of tyrosine-phosphorylated EGFR leads to tumorigenesis : The critical role of oxidative stress. / Goldkorn, Tzipora; Filosto, Simone; Chung, Samuel.
Vesicle Trafficking in Cancer. Vol. 9781461465287 Springer New York, 2013. p. 303-325.Research output: Chapter in Book/Report/Conference proceeding › Chapter
}
TY - CHAP
T1 - Stress-Driven endocytosis of tyrosine-phosphorylated EGFR leads to tumorigenesis
T2 - The critical role of oxidative stress
AU - Goldkorn, Tzipora
AU - Filosto, Simone
AU - Chung, Samuel
PY - 2013/7/1
Y1 - 2013/7/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84949177552&partnerID=8YFLogxK
U2 - 10.1007/978-1-4614-6528-7_15
DO - 10.1007/978-1-4614-6528-7_15
M3 - Chapter
SN - 1461465273
SN - 9781461465270
VL - 9781461465287
SP - 303
EP - 325
BT - Vesicle Trafficking in Cancer
PB - Springer New York
ER -