Evidence map›Paper›PMID 10477766›Full record

ArticleThe Journal of cell biology1999

Protein kinase C-dependent mobilization of the alpha6beta4 integrin from hemidesmosomes and its association with actin-rich cell protrusions drive the chemotactic migration of carcinoma cells.

I Rabinovitz, A Toker, A M Mercurio

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of cell biology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.

0numbers the graph read from it
0cells of the map it votes in
82citing papers in PubMed
4.1field-weighted citation impact, top 5% 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

82 citing papers in PubMed, 211 citations in OpenAlex.

  1. Coexpression of alpha6beta4 integrin and guanine nucleotide exchange factor Net1 identifies node-positive breast cancer patients at high risk for distant metastasis.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2009
    Trial
  2. Structure, function and usage of integrin alpha 6 (CD49f): A comprehensive review.Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia · 2026
    Review
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  11. Rapid phenotyping of cancer stem cells using multichannel nanosensor arrays.Nanomedicine : nanotechnology, biology, and medicine · 2018
    Article
  12. Classifying tumors by supervised network propagation.Bioinformatics (Oxford, England) · 2018
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22 more citing papers are in PubMed but not listed here.

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

3 authors at 2 institutions in 1 country.

I RabinovitzDepartment of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.
A Toker
A M Mercurio
Beth Israel Deaconess Medical Center · USBoston Biomedical Research Institute · US

Funding

INTEGRIN FUNCTION AND SIGNALING IN CARCINOMA PROGRESSIONR01CA080789 · NCI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI MERCURIO, ARTHUR M · 1999 to 2012
$4.7M
THE PATHOBIOLOGY OF COLORECTAL CANCERP01CA044704 · NCI · NEW ENGLAND DEACONESS HOSPITAL · PI KOLODNER, RICHARD D · 1987 to 1998
–
NCI NIH HHS CA44704NCI NIH HHS CA80789NCI NIH HHS R01 CA080789
6 · The paper itself

Abstract

We explored the hypothesis that the chemotactic migration of carcinoma cells that assemble hemidesmosomes involves the activation of a signaling pathway that releases the alpha6beta4 integrin from these stable adhesion complexes and promotes its association with F-actin in cell protrusions enabling it to function in migration. Squamous carcinoma-derived A431 cells were used because they express alpha6beta4 and migrate in response to EGF stimulation. Using function-blocking antibodies, we show that the alpha6beta4 integrin participates in EGF-stimulated chemotaxis and is required for lamellae formation on laminin-1. At concentrations of EGF that stimulate A431 chemotaxis ( approximately 1 ng/ml), the alpha6beta4 integrin is mobilized from hemidesmosomes as evidenced by indirect immunofluorescence microscopy using mAbs specific for this integrin and hemidesmosomal components and its loss from a cytokeratin fraction obtained by detergent extraction. EGF stimulation also increased the formation of lamellipodia and membrane ruffles that contained alpha6beta4 in association with F-actin. Importantly, we demonstrate that this mobilization of alpha6beta4 from hemidesmosomes and its redistribution to cell protrusions occurs by a mechanism that involves activation of protein kinase C-alpha and that it is associated with the phosphorylation of the beta4 integrin subunit on serine residues. Thus, the chemotactic migration of A431 cells on laminin-1 requires not only the formation of F-actin-rich cell protrusions that mediate alpha6beta4-dependent cell movement but also the disruption of alpha6beta4-containing hemidesmosomes by protein kinase C.

Indexed as

ChemotaxisActinsAntigens, SurfaceCarbazolesCarcinoma, Squamous CellCell MembraneCell SizeDesmosomesEnzyme ActivationEpidermal Growth FactorErbB ReceptorsHumansIndolesIntegrin alpha6beta4IntegrinsKeratinsActinsAntigens, SurfaceCarbazolesEpidermal Growth FactorErbB ReceptorsGo 6976IndolesIntegrin alpha6beta4IntegrinsKeratinsLamininPhosphoserinePhosphotyrosineProtein Kinase C

Identifiers

PMID10477766
PMCPMC2169473
OpenAlexW2165843111

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.