Evidence map›Paper›PMID 23792445›Full record

ArticleOncogene2014

Annexin A2 depletion delays EGFR endocytic trafficking via cofilin activation and enhances EGFR signaling and metastasis formation.

M de Graauw, L Cao, L Winkel, M H A M van Miltenburg, S E le Dévédec, M Klop, K Yan, C Pont, V-M Rogkoti, A Tijsma and 5 more

Abstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
3.0field-weighted citation impact, top 9% 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

38 citing papers in PubMed, 63 citations in OpenAlex.

  1. Article
  2. GDI2 protein: research progress and its mechanisms in diseases.Frontiers in cell and developmental biology · 2026
    Review
  3. Article
  4. Article
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  6. Article
  7. Aging · 2021
    Article
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  12. Review
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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 2 institutions in 1 country.

M de GraauwDivision of Toxicology, LACDR, Leiden University, Leiden, The Netherlands.
L CaoImaging and Bio-informatics group, LIACS, Leiden University, Leiden, The Netherlands.
L WinkelBiomechanics Laboratory, Erasmus MC, Rotterdam, The Netherlands.
M H A M van MiltenburgDepartment of Molecular Pathology, Netherland Cancer Institute, Amsterdam, The Netherlands.
S E le DévédecDivision of Toxicology, LACDR, Leiden University, Leiden, The Netherlands.
M KlopDivision of Toxicology, LACDR, Leiden University, Leiden, The Netherlands.
K YanImaging and Bio-informatics group, LIACS, Leiden University, Leiden, The Netherlands.
C PontDivision of Toxicology, LACDR, Leiden University, Leiden, The Netherlands.
V-M RogkotiDivision of Toxicology, LACDR, Leiden University, Leiden, The Netherlands.
A TijsmaDivision of Toxicology, LACDR, Leiden University, Leiden, The Netherlands.
A ChaudhuriDivision of Toxicology, LACDR, Leiden University, Leiden, The Netherlands.
R LalaiDivision of Toxicology, LACDR, Leiden University, Leiden, The Netherlands.
L PriceDivision of Toxicology, LACDR, Leiden University, Leiden, The Netherlands.
F VerbeekImaging and Bio-informatics group, LIACS, Leiden University, Leiden, The Netherlands.
B van de WaterDivision of Toxicology, LACDR, Leiden University, Leiden, The Netherlands.
Leiden University · NLErasmus University Rotterdam · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Enhanced epidermal growth factor receptor (EGFR) activity has been strongly linked to breast cancer progression and mediators of EGFR endocytosis may well be involved. We developed a semi-automated high-content fluorescence microscopy-based EGFR endocytosis screen to identify proteins that mediate EGFR endocytosis in human HBL100 breast cancer cells. Knockdown of 172 individual endocytosis and actin-regulatory genes with small interfering RNAs led to the identification of 14 genes of which the contribution to EGFR endocytosis in breast cancer is until now poorly defined, including DNAJC6, GDI2, FGD6, HAX1, NECAP2 and AnxA2. We show that depletion of the actin and endocytosis regulatory protein annexin A2 (AnxA2) in a panel of four triple negative breast cancer (TNBC) cell lines affected EGFR endocytosis. Depletion of AnxA2 in the aggressive and highly metastatic MDA-MB-231 TNBC cell line resulted in the inhibition of EGFR transport beyond the early endosomes. This inhibition coincided with enhanced epidermal growth factor (EGF)-induced cell migration and downstream signaling via c-Jun N-terminal kinase (JNK) and Akt. Moreover, AnxA2 knockdown increased lung metastasis formation in mice. The effect of AnxA2 knockdown on EGFR endocytosis in MDA-MB-231 was related to dephosphorylation/activation of the actin-severing protein cofilin, as re-expression of an inactive S3E-cofilin mutant, but not an active S3A-cofilin mutant, re-established EGFR endocytosis to control levels. Together, our data provide evidence for AnxA2 as a mediator of EGFR endocytosis and signaling in breast cancer via regulation of cofilin activation.

Indexed as

EndocytosisNeoplasm MetastasisSignal TransductionActin Depolymerizing FactorsAnimalsAnnexin A2Cell Line, TumorErbB ReceptorsGene Knockdown TechniquesHumansMiceMicroscopy, FluorescenceRNA InterferenceActin Depolymerizing FactorsAnnexin A2ANXA2 protein, humanErbB Receptors

Identifiers

PMID23792445
OpenAlexW2032240256

What OpenQuestion holds

Textmetadata
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.