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Emerging functions of the EGFR in cancer
- Source :
- Molecular Oncology, Vol 12, Iss 1, Pp 3-20 (2018), Molecular Oncology
- Publication Year :
- 2018
- Publisher :
- Wiley, 2018.
-
Abstract
- The physiological function of the epidermal growth factor receptor (EGFR) is to regulate epithelial tissue development and homeostasis. In pathological settings, mostly in lung and breast cancer and in glioblastoma, the EGFR is a driver of tumorigenesis. Inappropriate activation of the EGFR in cancer mainly results from amplification and point mutations at the genomic locus, but transcriptional upregulation or ligand overproduction due to autocrine/paracrine mechanisms has also been described. Moreover, the EGFR is increasingly recognized as a biomarker of resistance in tumors, as its amplification or secondary mutations have been found to arise under drug pressure. This evidence, in addition to the prominent function that this receptor plays in normal epithelia, has prompted intense investigations into the role of the EGFR both at physiological and at pathological level. Despite the large body of knowledge obtained over the last two decades, previously unrecognized (herein defined as 'noncanonical') functions of the EGFR are currently emerging. Here, we will initially review the canonical ligand-induced EGFR signaling pathway, with particular emphasis to its regulation by endocytosis and subversion in human tumors. We will then focus on the most recent advances in uncovering noncanonical EGFR functions in stress-induced trafficking, autophagy, and energy metabolism, with a perspective on future therapeutic applications.
- Subjects :
- 0301 basic medicine
Cancer Research
EGFR
Endosomes
Review Article
Biology
medicine.disease_cause
Ligands
lcsh:RC254-282
03 medical and health sciences
Mice
Downregulation and upregulation
Stress, Physiological
Neoplasms
Genetics
medicine
Autophagy
Animals
Humans
cancer
Epidermal growth factor receptor
Receptor
Autocrine signalling
Mice, Knockout
Point mutation
membrane trafficking
Cell Membrane
General Medicine
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Endocytosis
Cell biology
ErbB Receptors
030104 developmental biology
Oncology
biology.protein
Molecular Medicine
Signal transduction
Carcinogenesis
EGFR, cancer
signal transduction
Subjects
Details
- Language :
- English
- ISSN :
- 15747891 and 18780261
- Volume :
- 12
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Molecular Oncology
- Accession number :
- edsair.doi.dedup.....605170211bc0e3a9c3293cc512f6ed3e