Evidence map›Paper›PMID 26874904›Full record

ArticleInternational journal of cancer2016

PKM2 uses control of HuR localization to regulate p27 and cell cycle progression in human glioblastoma cells.

Joydeep Mukherjee, Shigeo Ohba, Wendy L See, Joanna J Phillips, Annette M Molinaro, Russell O Pieper

Open access · bronzeAbstract read
In one paragraph

Article in International journal of cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.6field-weighted citation impact, top 19% 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

19 citing papers in PubMed, 34 citations in OpenAlex.

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  5. Muscle-specific pyruvate kinase isoforms, PKM1 and PKM2, regulate mammalian SWI/SNF proteins and histone 3 phosphorylation during myoblast differentiation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024
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  19. Cell cycle RNA regulons coordinating early lymphocyte development.Wiley interdisciplinary reviews. RNA · 2017
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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

6 authors at 3 institutions in 1 country.

Joydeep MukherjeeThe Department of Neurological Surgery and the Brain Tumor Research Center, Helen Diller Family Comprehensive Cancer Center, University of California-San Francisco, San Francisco, CA, 94158.
Shigeo OhbaThe Department of Neurological Surgery and the Brain Tumor Research Center, Helen Diller Family Comprehensive Cancer Center, University of California-San Francisco, San Francisco, CA, 94158.
Wendy L SeeThe Department of Neurological Surgery and the Brain Tumor Research Center, Helen Diller Family Comprehensive Cancer Center, University of California-San Francisco, San Francisco, CA, 94158.
Joanna J PhillipsThe Department of Neurological Surgery and the Brain Tumor Research Center, Helen Diller Family Comprehensive Cancer Center, University of California-San Francisco, San Francisco, CA, 94158.
Annette M MolinaroThe Department of Neurological Surgery and the Brain Tumor Research Center, Helen Diller Family Comprehensive Cancer Center, University of California-San Francisco, San Francisco, CA, 94158.
Russell O PieperThe Department of Neurological Surgery and the Brain Tumor Research Center, Helen Diller Family Comprehensive Cancer Center, University of California-San Francisco, San Francisco, CA, 94158.
Neurological Surgery · USUniversity of California, San Francisco · USUCSF Helen Diller Family Comprehensive Cancer Center · US

Funding

Understanding the role of altered metabolism in gliomagenesisR01CA171610 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI PIEPER, RUSSELL O. · 2013 to 2017
$1.6M
NCI NIH HHS R01 CA171610
6 · The paper itself

Abstract

The M2 isoform of pyruvate kinase (PK) is upregulated in most cancers including glioblastoma. Although PKM2 has been reported to use dual kinase activities to regulate cell growth, it also interacts with phosphotyrosine (pY)-containing peptides independently of its kinase activity. The potential for PKM2 to use the binding of pY-containing proteins to control tumor growth has not been fully examined. We here describe a novel mechanism by which PKM2 interacts in the nucleus with the RNA binding protein HuR to regulate HuR sub-cellular localization, p27 levels, cell cycle progression and glioma cell growth. Suppression of PKM2 in U87, T98G and LN319 glioma cells resulted in increased p27 levels, defects in entry into mitosis, increased centrosome number, and decreased cell growth. These effects could be reversed by shRNA targeting p27. The increased levels of p27 in PKM2 knock-down cells were caused by a loss of the nuclear interaction between PKM2 and HuR, and a subsequent cytoplasmic re-distribution of HuR, which in turn led to increased cap-independent p27 mRNA translation. Consistent with these results, the alterations in p27 mRNA translation, cell cycle progression and cell growth caused by PKM2 suppression could be reversed in vitro and in vivo by suppression of HuR or p27 levels, or by introduction of forms of PKM2 that could bind pY, regardless of their kinase activity. These results define a novel mechanism by which PKM2 regulates glioma cell growth, and also define a novel set of potential therapeutic targets along the PKM2-HuR-p27 pathway.

Indexed as

Carrier ProteinsCell CycleCell Line, TumorCell ProliferationELAV-Like Protein 1Gene Expression Regulation, NeoplasticGlioblastomaHumansMembrane ProteinsProliferating Cell Nuclear AntigenRNA, MessengerRNA, Small InterferingThyroid Hormone-Binding ProteinsThyroid HormonesCarrier ProteinsELAVL1 protein, humanELAV-Like Protein 1Membrane Proteinsp27 antigenProliferating Cell Nuclear AntigenRNA, MessengerRNA, Small InterferingThyroid Hormone-Binding ProteinsThyroid Hormonescell cycleHuRmetabolismp27pyruvate kinase

Identifiers

PMID26874904
PMCPMC6615049
OpenAlexW2255930458

What OpenQuestion holds

Textmetadata
LicenceTDM
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.