Emerging functions of the EGFR in cancer
By S. Sigismund, D. Avanzato, Letizia Lanzetti. Molecular Oncology, 2017
1,295 citations recorded by the source corpus.
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.
Subfields: Cancer Research, Oncology, Pulmonary and Respiratory Medicine
View Paper: https://www.semanticscholar.org/paper/4d530fdbe37661ed2637a67418b4371133690b78
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Citations in the corpus
- Nanoparticle-Based Drug Delivery in Cancer Therapy and Its Role in Overcoming Drug Resistance (2020, background): “Results indicated that the expression of anti-apoptotic genes was downregulated, while the ABC-transporter markers were inhibited (Singh et al., 2018).”
- JMJD8 Promotes Malignant Progression of Lung Cancer by Maintaining EGFR Stability and EGFR/PI3K/AKT Pathway Activation (2021, background): “EGFR internalization processes can be divided into ligand-dependent processes or non-ligand-dependent processes [25]; ligand-mediated EGFR activation is achieved by conformational changes in the receptor’s extracellular domain after ligand binding [26].”