Evidence map›Paper›PMID 26936397›Full record

ArticleNeoplasia (New York, N.Y.)2016

Ezrin Enhances EGFR Signaling and Modulates Erlotinib Sensitivity in Non-Small Cell Lung Cancer Cells.

Yasemin Saygideğer-Kont, Tsion Zewdu Minas, Hayden Jones, Sarah Hour, Haydar Çelik, Idil Temel, Jenny Han, Nese Atabey, Hayriye Verda Erkizan, Jeffrey A Toretsky and 1 more

Open access · goldAbstract read
In one paragraph

Article in Neoplasia (New York, N.Y.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
1.8field-weighted citation impact, top 16% 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

24 citing papers in PubMed, 46 citations in OpenAlex.

  1. Downregulation ofJournal of thoracic disease · 2026
    Article
  2. ERM Inhibition Confers Ferroptosis Resistance through ROS-Induced NRF2 Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  3. Beyond the membrane: rethinking EGFR signaling in physiology and cancer.Cellular and molecular life sciences : CMLS · 2026
    Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. Pathophysiological Roles of Actin-Binding Scaffold Protein, Ezrin.International journal of molecular sciences · 2022
    Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
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

11 authors at 3 institutions in 2 countries.

Yasemin Saygideğer-KontDepartment of Oncology, Georgetown University Medical Center, Washington, DC, USA; Department of Molecular Medicine, Institute of Health Sciences, Dokuz Eylul University, Izmir, Turkey.
Tsion Zewdu MinasDepartment of Oncology, Georgetown University Medical Center, Washington, DC, USA.
Hayden JonesDepartment of Oncology, Georgetown University Medical Center, Washington, DC, USA.
Sarah HourDepartment of Oncology, Georgetown University Medical Center, Washington, DC, USA.
Haydar ÇelikDepartment of Oncology, Georgetown University Medical Center, Washington, DC, USA.
Idil TemelDepartment of Oncology, Georgetown University Medical Center, Washington, DC, USA.
Jenny HanDepartment of Oncology, Georgetown University Medical Center, Washington, DC, USA.
Nese AtabeyDepartment of Medical Biology, Dokuz Eylul University School of Medicine, Izmir, Turkey.
Hayriye Verda ErkizanDepartment of Oncology, Georgetown University Medical Center, Washington, DC, USA.
Jeffrey A ToretskyDepartment of Oncology, Georgetown University Medical Center, Washington, DC, USA.
Aykut ÜrenDepartment of Oncology, Georgetown University Medical Center, Washington, DC, USA. Electronic address: au26@georgetown.edu.
Georgetown University Medical Center · USGeorgetown University · USDokuz Eylül University · TR

Funding

Tissue Culture Shared ResourceP30CA051008 · NCI · GEORGETOWN UNIVERSITY · PI Louis M Weiner · 1990 to 2026
$71.5M
NCI NIH HHS P30 CA051008NCI NIH HHS P30 CA51008
6 · The paper itself

Abstract

Ezrin is a scaffolding protein that is involved in oncogenesis by linking cytoskeletal and membrane proteins. Ezrin interacts with epidermal growth factor receptor (EGFR) in the cell membrane, but little is known about the effects of this interaction on EGFR signaling pathway. In this study, we established the biological and functional significance of ezrin-EGFR interaction in non-small cell lung cancer (NSCLC) cells. Endogenous ezrin and EGRF interaction was confirmed by co-immunoprecipitation and immunofluorescent staining. When expression of ezrin was inhibited, EGFR activity and phosphorylation levels of downstream signaling pathway proteins ERK and STAT3 were decreased. Cell fractionation experiments revealed that nuclear EGFR was significantly diminished in ezrin-knockdown cells. Consequently, mRNA levels of EGFR target genes AURKA, COX-2, cyclin D1, and iNOS were decreased in ezrin-depleted cells. A small molecule inhibitor of ezrin, NSC305787, reduced EGF-induced phosphorylation of EGFR and downstream target proteins, EGFR nuclear translocation, and mRNA levels of nuclear EGFR target genes similar to ezrin suppression. NSC305787 showed synergism with erlotinib in wild-type EGFR-expressing NSCLC cells, whereas no synergy was observed in EGFR-null cells. Phosphorylation of ezrin on Y146 was found as an enhancer of ezrin-EGFR interaction and required for increased proliferation, colony formation, and drug resistance to erlotinib. These findings suggest that ezrin-EGFR interaction augments oncogenic functions of EGFR and that targeting ezrin may provide a potential novel approach to overcome erlotinib resistance in NSCLC cells.

Indexed as

ApoptosisCarcinoma, Non-Small-Cell LungCell Line, TumorCytoskeletal ProteinsDrug Resistance, NeoplasmErbB ReceptorsErlotinib HydrochlorideEzrinHumansMutationNeoplasm ProteinsPhosphorylationProtein BindingProtein Kinase InhibitorsSignal TransductionSTAT3 Transcription FactorCytoskeletal ProteinsEGFR protein, humanErbB ReceptorsErlotinib HydrochlorideEzrinNeoplasm ProteinsProtein Kinase InhibitorsSTAT3 Transcription Factor

Identifiers

PMID26936397
PMCPMC5005263
OpenAlexW2291970687

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.