Next Article in Journal
Physical Activity and Quality of Life in Cancer Survivors: A Meta-Synthesis of Qualitative Research
Previous Article in Journal
A Feasibility Study of Personalized Prescription Schemes for Glioblastoma Patients Using a Proliferation and Invasion Glioma Model
Previous Article in Special Issue
HER2 in Breast Cancer Stemness: A Negative Feedback Loop towards Trastuzumab Resistance
Article Menu
Issue 5 (May) cover image

Export Article

Open AccessReview
Cancers 2017, 9(5), 52; doi:10.3390/cancers9050052

Epidermal Growth Factor Receptor Cell Proliferation Signaling Pathways

Department of Medical Genetics and Signal Transduction Research Group, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2H7, Canada
*
Author to whom correspondence should be addressed.
Academic Editor: Samuel C. Mok
Received: 7 April 2017 / Revised: 10 May 2017 / Accepted: 10 May 2017 / Published: 17 May 2017
(This article belongs to the Special Issue EGFR Family Signaling in Cancer)
View Full-Text   |   Download PDF [2311 KB, uploaded 17 May 2017]   |  

Abstract

The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that is commonly upregulated in cancers such as in non-small-cell lung cancer, metastatic colorectal cancer, glioblastoma, head and neck cancer, pancreatic cancer, and breast cancer. Various mechanisms mediate the upregulation of EGFR activity, including common mutations and truncations to its extracellular domain, such as in the EGFRvIII truncations, as well as to its kinase domain, such as the L858R and T790M mutations, or the exon 19 truncation. These EGFR aberrations over-activate downstream pro-oncogenic signaling pathways, including the RAS-RAF-MEK-ERK MAPK and AKT-PI3K-mTOR pathways. These pathways then activate many biological outputs that are beneficial to cancer cell proliferation, including their chronic initiation and progression through the cell cycle. Here, we review the molecular mechanisms that regulate EGFR signal transduction, including the EGFR structure and its mutations, ligand binding and EGFR dimerization, as well as the signaling pathways that lead to G1 cell cycle progression. We focus on the induction of CYCLIN D expression, CDK4/6 activation, and the repression of cyclin-dependent kinase inhibitor proteins (CDKi) by EGFR signaling pathways. We also discuss the successes and challenges of EGFR-targeted therapies, and the potential for their use in combination with CDK4/6 inhibitors. View Full-Text
Keywords: epidermal growth factor receptor; ErBB; signal transduction; ERK; AKT; cell cycle; cell proliferation; G1 epidermal growth factor receptor; ErBB; signal transduction; ERK; AKT; cell cycle; cell proliferation; G1
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Wee, P.; Wang, Z. Epidermal Growth Factor Receptor Cell Proliferation Signaling Pathways. Cancers 2017, 9, 52.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Cancers EISSN 2072-6694 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top