Epidermal Growth Factor Receptor Cell Proliferation Signaling Pathways

Wee, Ping; Wang, Zhixiang

doi:10.3390/cancers9050052

Cited by 2,027HER2/EGFR in Cancer ResearchLung Cancer Treatments and MutationsProtein Kinase Regulation and GTPase Signaling

Epidermal Growth Factor Receptor Cell Proliferation Signaling Pathways

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Wee, Ping, Wang, Zhixiang·2017·Cancers

DOI 10.3390/cancers9050052PMC PMC5447962

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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.

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MUSE has been used in several studies.
“and has been used in several studies (Habes et al., 2016; Satterthwaite et al., 2016; Wee 2017; Tian et al., 2018).”
From A comparison of Freesurfer and multi-atlas MUSE for brain anatomy segmentation: Findings about size and age bias, and inter-scanner stability in multi-site aging studies (2020) · cites this paper as Wee 2017
The cited paper’s Signal Transduction section discusses EGFR signaling and cell proliferation, not use of MUSE. Searches for “MUSE” and its neuroimaging-segmentation context returned no relevant passage in our copy, so this source does not verify the attributed claim. (LLM, conf=0.77)
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Authors: Wee, P., & Wang, Z.
Affiliations: University of Alberta (CA)
Corresponding author: Wang, Zhixiang
ORCID: Wee, Ping
Wang, Zhixiang
Venue: Cancers
Publisher: MDPI AG
Published: 2017-05-17
Volume: 9
Issue: 5
Pages: 52
ISSN: 2072-6694 (ISSN-L)
DOI: 10.3390/cancers9050052
PMC: PMC5447962
OpenAlex: W2615601352
Cited by: 2,027
References: 38
Citations by year: 2026: 219 · 2025: 323 · 2024: 305 · 2023: 271 · 2022: 268 · 2021: 221 · 2020: 197 · 2019: 130 · 2018: 77 · 2017: 13 · 2013: 1
FWCI: 11.96
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Cancers (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: University of Alberta
Natural Sciences and Engineering Research Council of Canada
Topics: Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords: epidermal growth factor receptor, EGFR mutation, EGFRvIII, L858R mutation, T790M mutation, EGFR signaling, MAPK signaling, PI3K/AKT/mTOR pathway, EGFR dimerization, ligand binding, G1 cell cycle progression, cyclin D, CDK4/6, cyclin-dependent kinase inhibitors, anti-EGFR therapy, tumor cell proliferation

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