Evidence map›Paper›PMID 28320862›Full record

ArticleThe Journal of biological chemistry2017

Differential involvement of the microtubule cytoskeleton in insulin receptor substrate 1 (IRS-1) and IRS-2 signaling to AKT determines the response to microtubule disruption in breast carcinoma cells.

Jose Mercado-Matos, Jennifer L Clark, Andrew J Piper, Jenny Janusis, Leslie M Shaw

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
0.9field-weighted citation impact, top 27% 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

13 citing papers in PubMed, 24 citations in OpenAlex.

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  4. Inhibition of LAR attenuates neuroinflammation through RhoA/IRS-1/Akt signaling pathway after intracerebral hemorrhage in mice.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023
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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

5 authors at 1 institution in 1 country.

Jose Mercado-MatosFrom the Department of Molecular, Cell, and Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605.
Jennifer L ClarkFrom the Department of Molecular, Cell, and Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605.
Andrew J PiperFrom the Department of Molecular, Cell, and Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605.
Jenny JanusisFrom the Department of Molecular, Cell, and Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605.
Leslie M ShawFrom the Department of Molecular, Cell, and Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605 leslie.shaw@umassmed.edu.
University of Massachusetts Chan Medical School · US

Funding

IRS-2 Function in Tumor Progression and MetastasisR01CA142782 · NCI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI SHAW, LESLIE M · 2010 to 2014
$1.6M
The Impact of IRS2-microtubule interactions in the progression of breast cancerF31CA180706 · NCI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI MERCADO-MATOS, JOSE RAUL · 2013 to 2016
$118k
NCI NIH HHS F31 CA180706NCI NIH HHS R01 CA142782
6 · The paper itself

Abstract

The insulin receptor substrate (IRS) proteins serve as essential signaling intermediates for the activation of PI3K by both the insulin-like growth factor 1 receptor (IGF-1R) and its close family member, the insulin receptor (IR). Although IRS-1 and IRS-2 share significant homology, they regulate distinct cellular responses downstream of these receptors and play divergent roles in breast cancer. To investigate the mechanism by which signaling through IRS-1 and IRS-2 results in differential outcomes, we assessed the involvement of the microtubule cytoskeleton in IRS-dependent signaling. Treatment with drugs that either stabilize or disrupt microtubules reveal that an intact microtubule cytoskeleton contributes to IRS-2- but not IRS-1-mediated activation of AKT by IGF-1. Proximal IGF-1R signaling events, including IRS tyrosine phosphorylation and recruitment of PI3K, are not inhibited by microtubule disruption, indicating that IRS-2 requires the microtubule cytoskeleton at the level of downstream effector activation. IRS-2 colocalization with tubulin is enhanced upon Taxol-mediated microtubule stabilization, which, together with the signaling data, suggests that the microtubule cytoskeleton may facilitate access of IRS-2 to downstream effectors such as AKT. Of clinical relevance is that our data reveal that expression of IRS-2 sensitizes breast carcinoma cells to apoptosis in response to treatment with microtubule-disrupting drugs, identifying IRS-2 as a potential biomarker for the response of breast cancer patients to

Indexed as

Biomarkers, TumorBreast NeoplasmsCell CycleCell Line, TumorCytoskeletonFemaleHumansInsulin Receptor Substrate ProteinsMicroscopy, FluorescenceMicrotubulesPaclitaxelPhosphorylationProtein TransportProto-Oncogene Proteins c-aktReceptor, IGF Type 1Receptors, SomatomedinAKT1 protein, humanBiomarkers, TumorIGF1R protein, humanInsulin Receptor Substrate ProteinsIRS1 protein, humanIRS2 protein, humanPaclitaxelProto-Oncogene Proteins c-aktReceptor, IGF Type 1Receptors, SomatomedinTubulinTyrosineAkt PKBapoptosisbreast cancercell signalinginsulin receptor substrate 1 (IRS-1)insulin receptor substrate 2 (IRS-2)microtubule

Identifiers

PMID28320862
PMCPMC5427262
OpenAlexW2597578304

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.