Evidence map›Paper›PMID 26282580›Full record

ArticleJournal of cellular and molecular medicine2015

Doxycycline reduces the migration of tuberous sclerosis complex-2 null cells - effects on RhoA-GTPase and focal adhesion kinase.

Ho Yin Ng, Brian Gregory George Oliver, Janette Kay Burgess, Vera P Krymskaya, Judith Lee Black, Lyn M Moir

Open access · goldAbstract read
In one paragraph

Article in Journal of cellular and molecular medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.6field-weighted citation impact, top 31% 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

3 citing papers in PubMed, 9 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
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

6 authors at 3 institutions in 2 countries.

Ho Yin NgSydney Medical School, Discipline of Pharmacology, University of Sydney, Sydney, NSW, Australia.
Brian Gregory George OliverSydney Medical School, Discipline of Pharmacology, University of Sydney, Sydney, NSW, Australia.
Janette Kay BurgessSydney Medical School, Discipline of Pharmacology, University of Sydney, Sydney, NSW, Australia.
Vera P KrymskayaDepartment of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Judith Lee BlackSydney Medical School, Discipline of Pharmacology, University of Sydney, Sydney, NSW, Australia.
Lyn M MoirSydney Medical School, Discipline of Pharmacology, University of Sydney, Sydney, NSW, Australia.
University of Sydney · AUUniversity of Pennsylvania · USWoolcock Institute of Medical Research · AU

Funding

Role of folliculin (FLCN) in lung cell survivalR01HL110551 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI KRYMSKAYA, VERA P · 2012 to 2015
$1.8M
The Role of TSC2 and Rho GTPases in LAMR01HL090829 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI KRYMSKAYA, VERA P · 2008 to 2011
$1.6M
NHLBI NIH HHS R01HL090829NHLBI NIH HHS R01 HL110551
6 · The paper itself

Abstract

Lymphangioleiomyomatosis (LAM) is associated with dysfunction of the tuberous sclerosis complex (TSC) leading to enhanced cell proliferation and migration. This study aims to examine whether doxycycline, a tetracycline antibiotic, can inhibit the enhanced migration of TSC2-deficient cells, identify signalling pathways through which doxycycline works and to assess the effectiveness of combining doxycycline with rapamycin (mammalian target of rapamycin complex 1 inhibitor) in controlling cell migration, proliferation and wound closure. TSC2-positive and TSC2-negative mouse embryonic fibroblasts (MEF), 323-TSC2-positive and 323-TSC2-null MEF and Eker rat uterine leiomyoma (ELT3) cells were treated with doxycycline or rapamycin alone, or in combination. Migration, wound closure and proliferation were assessed using a transwell migration assay, time-lapse microscopy and manual cell counts respectively. RhoA-GTPase activity, phosphorylation of p70S6 kinase (p70S6K) and focal adhesion kinase (FAK) in TSC2-negative MEF treated with doxycycline were examined using ELISA and immunoblotting techniques. The enhanced migration of TSC2-null cells was reduced by doxycycline at concentrations as low as 20 pM, while the rate of wound closure was reduced at 2-59 μM. Doxycycline decreased RhoA-GTPase activity and phosphorylation of FAK in these cells but had no effect on the phosphorylation of p70S6K, ERK1/2 or AKT. Combining doxycycline with rapamycin significantly reduced the rate of wound closure at lower concentrations than achieved with either drug alone. This study shows that doxycycline inhibits TSC2-null cell migration. Thus doxycycline has potential as an anti-migratory agent in the treatment of diseases with TSC2 dysfunction.

Indexed as

AnimalsDoxycyclineFocal Adhesion Kinase 2LymphangioleiomyomatosisMiceRatsrho-Associated KinasesSirolimusTuberous SclerosisDoxycyclineFocal Adhesion Kinase 2rho-Associated KinasesSirolimusdoxycyclinefocal adhesion kinasemigrationpulmonary lymphangioleiomyomatosisrapamycinRhoA-GTPasetuberous sclerosis gene complex-2wound closure

Identifiers

PMID26282580
PMCPMC4627568
OpenAlexW1956535582

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.