Evidence map›Paper›PMID 36524361›Full record

ArticleInternational journal of oncology2023

Upregulation of the EGFR/MEK1/MAPK1/2 signaling axis as a mechanism of resistance to antiestrogen‑induced BimEL dependent apoptosis in ER

Mackenzie L Hagan, Suchreet Mander, Carol Joseph, Michael McGrath, Amanda Barrett, Allison Lewis, William D Hill, Darren Browning, Meghan E McGee-Lawrence, Haifeng Cai and 5 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in International journal of oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.1field-weighted citation impact, top 22% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 9 citations in OpenAlex.

  1. Integrating Network Pharmacology andCombinatorial chemistry & high throughput screening · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 3 institutions in 1 country.

Mackenzie L HaganDepartment of Cellular Biology and Anatomy, Augusta University, Augusta, GA 30912, USA.
Suchreet ManderDepartment of Cellular Biology and Anatomy, Augusta University, Augusta, GA 30912, USA.
Carol JosephDepartment of Cellular Biology and Anatomy, Augusta University, Augusta, GA 30912, USA.
Michael McGrathDepartment of Cellular Biology and Anatomy, Augusta University, Augusta, GA 30912, USA.
Amanda BarrettDepartment of Pathology, Augusta University, Augusta, GA 30912, USA.
Allison LewisDepartment of Cellular Biology and Anatomy, Augusta University, Augusta, GA 30912, USA.
William D HillDepartment of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC 29425, USA.
Darren BrowningMedical College of Georgia Cancer Center, Augusta University, Augusta, GA 30912, USA.
Meghan E McGee-LawrenceDepartment of Cellular Biology and Anatomy, Augusta University, Augusta, GA 30912, USA.
Haifeng CaiDepartment of Cellular Biology and Anatomy, Augusta University, Augusta, GA 30912, USA.
Kebin LiuMedical College of Georgia Cancer Center, Augusta University, Augusta, GA 30912, USA.
John T BarrettMedical College of Georgia Cancer Center, Augusta University, Augusta, GA 30912, USA.
David A GewirtzDepartment of Pharmacology and Toxicology, Massey Cancer Center, Richmond, VA 23298, USA.
Muthusamy ThangarajuDepartment of Cellular Biology and Anatomy, Augusta University, Augusta, GA 30912, USA.
Patricia V SchoenleinDepartment of Cellular Biology and Anatomy, Augusta University, Augusta, GA 30912, USA.
Augusta University · USMedical University of South Carolina · USVirginia Cancer Institute · US

Funding

Kynurenine Pathway Regulation of CNS Senescence in Alzheimer's Disease PathologyR01AG067510 · NIA · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI HILL, WILLIAM D, MCGEE-LAWRENCE, MEGHAN E. · 2020 to 2023
$2.4M
Use of senolytics to enhance chemotherapeutic efficacy in lung cancerR01CA239706 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI GEWIRTZ, DAVID A., HARADA, HISASHI · 2019 to 2023
$2.0M
Antiestrogen-induced autophagy: a mechanism of cell survival in ER+ breast cancerR01CA121438 · NCI · AUGUSTA UNIVERSITY · PI SCHOENLEIN, PATRICIA V · 2008 to 2010
$915k
NCI NIH HHS R01 CA121438NCI NIH HHS R01 CA239706NIA NIH HHS R01 AG067510
6 · The paper itself

Abstract

The epidermal growth factor receptor (EGFR) is commonly upregulated in multiple cancer types, including breast cancer. In the present study, evidence is provided in support of the premise that upregulation of the EGFR/MEK1/MAPK1/2 signaling axis during antiestrogen treatment facilitates the escape of breast cancer cells from BimEL‑dependent apoptosis, conferring resistance to therapy. This conclusion is based on the findings that ectopic BimEL cDNA overexpression and confocal imaging studies confirm the pro‑apoptotic role of BimEL in ERα expressing breast cancer cells and that upregulated EGFR/MEK1/MAPK1/2 signaling blocks BimEL pro‑apoptotic action in an antiestrogen‑resistant breast cancer cell model. In addition, the present study identified a pro‑survival role for autophagy in antiestrogen resistance while EGFR inhibitor studies demonstrated that a significant percentage of antiestrogen‑resistant breast cancer cells survive EGFR targeting by pro‑survival autophagy. These pre‑clinical studies establish the possibility that targeting both the MEK1/MAPK1/2 signaling axis and pro‑survival autophagy may be required to eradicate breast cancer cell survival and prevent the development of antiestrogen resistance following hormone treatments. The present study uniquely identified EGFR upregulation as one of the mechanisms breast cancer cells utilize to evade the cytotoxic effects of antiestrogens mediated through BimEL‑dependent apoptosis.

Indexed as

ApoptosisBreast NeoplasmsDrug Resistance, NeoplasmEstrogen Receptor ModulatorsBcl-2-Like Protein 11Cell Line, TumorErbB ReceptorsFemaleHumansMitogen-Activated Protein Kinase 1Signal TransductionUp-RegulationBcl-2-Like Protein 11EGFR protein, humanErbB ReceptorsEstrogen Receptor ModulatorsMAPK1 protein, humanMitogen-Activated Protein Kinase 1antiestrogenantiestrogen resistanceantiprogestinapoptosisBimELbreast cancerEGFRMEK1/MAPK1/2 inhibitorspro‑survival autophagysenescence

Identifiers

PMID36524361
PMCPMC9854236
OpenAlexW4312211730

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.