Evidence map›Paper›PMID 29268862›Full record

ArticleeLife2017

EGF receptor signaling, phosphorylation, ubiquitylation and endocytosis in tumors in vivo.

Itziar Pinilla-Macua, Alexandre Grassart, Umamaheswar Duvvuri, Simon C Watkins, Alexander Sorkin

Open access · goldAbstract read
In one paragraph

Article in eLife, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.

0numbers the graph read from it
0cells of the map it votes in
70citing papers in PubMed
3.0field-weighted citation impact, top 8% 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

70 citing papers in PubMed, 110 citations in OpenAlex.

  1. Review
  2. Small-molecule CBLB inhibitor abolishes EGFR ubiquitination, reduces receptor endocytosis, and diminishes cell motility signaling.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  3. Article
  4. Beyond the membrane: rethinking EGFR signaling in physiology and cancer.Cellular and molecular life sciences : CMLS · 2026
    Review
  5. Article
  6. A neuregulin-like ligand and EGF receptor underpinFrontiers in cellular and infection microbiology · 2026
    Article
  7. Article
  8. Emergent eukaryotic directional sensing via receptor degradation and diffusion.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
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  19. Cryo-electron tomography pipeline for plasma membranes.bioRxiv : the preprint server for biology · 2024
    Article
  20. Article

10 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 2 countries.

Itziar Pinilla-MacuaDepartment of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, United States.
Alexandre GrassartDepartment of Molecular Microbial Pathogenesis, Institute Pasteur, Paris, France.
Umamaheswar DuvvuriDepartment of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, United States.
Simon C WatkinsDepartment of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, United States.
Alexander SorkinDepartment of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, United States.ORCID 0000-0002-4446-1920
University of Pittsburgh · USInstitut Pasteur · FR

Funding

PATHOGENESIS OF CANCER--ROLE OF EGF RECEPTOR ENDOCYTOSISR01CA089151 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SORKIN, ALEXANDER D · 2001 to 2023
$6.9M
Signaling by the EGF Receptor from EndosomesR01GM124186 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SORKIN, ALEXANDER D · 2017 to 2021
$1.6M
Novel targets to treat head and neck cancer in VeteransI01BX003456 · VA · VETERANS HEALTH ADMINISTRATION · PI DUVVURI, UMAMAHESWAR · 2017 to 2021
–
BLRD VA I01 BX003456NCI NIH HHS R01 CA089151NIGMS NIH HHS R01 GM124186
6 · The paper itself

Abstract

Despite a well-established role for the epidermal growth factor receptor (EGFR) in tumorigenesis, EGFR activities and endocytosis in tumors in vivo have not been studied. We labeled endogenous EGFR with GFP by genome-editing of human oral squamous cell carcinoma cells, which were used to examine EGFR-GFP behavior in mouse tumor xenografts in vivo. Intravital multiphoton imaging, confocal imaging of cryosections and biochemical analysis revealed that localization and trafficking patterns, as well as levels of phosphorylation and ubiquitylation of EGFR in tumors in vivo closely resemble patterns and levels observed in the same cells treated with 20-200 pM EGF in vitro. Consistent with the prediction of low ligand concentrations in tumors, EGFR endocytosis was kinase-dependent and blocked by inhibitors of clathrin-mediated internalization; and EGFR activity was insensitive to Cbl overexpression. Collectively, our data suggest that a small pool of active EGFRs is sufficient to drive tumorigenesis by signaling primarily through the Ras-MAPK pathway.

Indexed as

EndocytosisProtein Processing, Post-TranslationalSignal TransductionUbiquitinationAnimalsCarcinoma, Squamous CellCell Line, TumorDisease Models, AnimalErbB ReceptorsHeterograftsHumansMiceNeoplasm TransplantationPhosphorylationErbB Receptorscell biologyEGF receptorendocytosishumanmousetumour

Identifiers

PMID29268862
PMCPMC5741375
OpenAlexW2769423727

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.