Evidence map›Paper›PMID 22397367›Full record

ArticleBMC cancer2012

Ezrin phosphorylation on tyrosine 477 regulates invasion and metastasis of breast cancer cells.

Hannah Mak, Alexandra Naba, Sonal Varma, Colleen Schick, Andrew Day, Sandip K SenGupta, Monique Arpin, Bruce E Elliott

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
–field-weighted citation impact, top 95% 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

28 citing papers in PubMed, 3 citations in OpenAlex.

  1. Article
  2. The RNA-binding protein YTHDF3 affects gastric cancer cell migration and response to paclitaxel by regulating EZRIN.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2025
    Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Pathophysiological Roles of Actin-Binding Scaffold Protein, Ezrin.International journal of molecular sciences · 2022
    Review
  8. Review
  9. Review
  10. ARHGEF10L Promotes Cervical Tumorigenesis via RhoA-Mediated Signaling.Evidence-based complementary and alternative medicine : eCAM · 2021
    Article
  11. Article
  12. Review
  13. Bidirectional Tumor-Promoting Activities of Macrophage Ezrin.International journal of molecular sciences · 2020
    Article
  14. Article
  15. Ezrin Mediates Invasion and Metastasis in Tumorigenesis: A Review.Frontiers in cell and developmental biology · 2020
    Review
  16. Article
  17. [Investigation of the influence of mechanical signals on the structure of CD44/FERM complex via molecular dynamics simulation].Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi · 2018
    Article
  18. Review
  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

8 authors at 2 institutions in 3 countries.

Hannah MakDivision of Cancer Biology and Genetics, Cancer Research Institute, Queen's University, Kingston, ON, K7L 3N6, Canada.
Alexandra Naba
Sonal Varma
Colleen Schick
Andrew Day
Sandip K SenGupta
Monique Arpin
Bruce E Elliott
Queen's University · CACentre National de la Recherche Scientifique · FR

Funding

Canadian Institutes of Health Research 102644
6 · The paper itself

Abstract

backgroundThe membrane cytoskeletal crosslinker, ezrin, a member of the ERM family of proteins, is frequently over-expressed in human breast cancers, and is required for motility and invasion of epithelial cells. Our group previously showed that ezrin acts co-operatively with the non-receptor tyrosine kinase, Src, in deregulation of cell-cell contacts and scattering of epithelial cells. In particular, ezrin phosphorylation on Y477 by Src is specific to ezrin within the ERM family, and is required for HGF-induced scattering of epithelial cells. We therefore sought to examine the role of Y477 phosphorylation in ezrin on tumor progression.

methodsUsing a highly metastatic mouse mammary carcinoma cell line (AC2M2), we tested the effect of over-expressing a non-phosphorylatable form of ezrin (Y477F) on invasive colony growth in 3-dimensional Matrigel cultures, and on local invasion and metastasis in an orthotopic engraftment model.

resultsAC2M2 cells over-expressing Y477F ezrin exhibited delayed migration in vitro, and cohesive round colonies in 3-dimensional Matrigel cultures, compared to control cells that formed invasive colonies with branching chains of cells and numerous actin-rich protrusions. Moreover, over-expression of Y477F ezrin inhibits local tumor invasion in vivo. Whereas orthotopically injected wild type AC2M2 tumor cells were found to infiltrate into the abdominal wall and visceral organs within three weeks, tumors expressing Y477F ezrin remained circumscribed, with little invasion into the surrounding stroma and abdominal wall. Additionally, Y477F ezrin reduces the number of lung metastatic lesions.

conclusionsOur study implicates a role of Y477 ezrin, which is phosphorylated by Src, in regulating local invasion and metastasis of breast carcinoma cells, and provides a clinically relevant model for assessing the Src/ezrin pathway as a potential prognostic/predictive marker or treatment target for invasive human breast cancer.

Indexed as

AnimalsBlotting, WesternBreast NeoplasmsCarcinomaCell MovementCytoskeletal ProteinsEzrinFemaleMiceMice, NudeNeoplasm InvasivenessNeoplasm MetastasisPhosphorylationTumor Cells, CulturedTyrosineCytoskeletal ProteinsEzrinTyrosine

Identifiers

PMID22397367
PMCPMC3372425
OpenAlexW1601224168

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.