Evidence map›Paper›PMID 26183399›Full record

ArticleOncotarget2015

Targeting stromal-induced pyruvate kinase M2 nuclear translocation impairs oxphos and prostate cancer metastatic spread.

Elisa Giannoni, Maria Letizia Taddei, Andrea Morandi, Giuseppina Comito, Maura Calvani, Francesca Bianchini, Barbara Richichi, Giovanni Raugei, Nicholas Wong, Damu Tang and 1 more

Open access · diamondAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed
4.6field-weighted citation impact, top 4% 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

64 citing papers in PubMed, 109 citations in OpenAlex.

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  10. Lactate and lactylation in cancer.Signal transduction and targeted therapy · 2025
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  15. Mitochondrial transfer in tunneling nanotubes-a new target for cancer therapy.Journal of experimental & clinical cancer research : CR · 2024
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4 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

11 authors at 2 institutions in 2 countries.

Elisa GiannoniDepartment of Experimental and Clinical Biomedical Sciences, University of Florence, 50134, Florence, Italy.
Maria Letizia TaddeiDepartment of Experimental and Clinical Biomedical Sciences, University of Florence, 50134, Florence, Italy.
Andrea MorandiDepartment of Experimental and Clinical Biomedical Sciences, University of Florence, 50134, Florence, Italy.
Giuseppina ComitoDepartment of Experimental and Clinical Biomedical Sciences, University of Florence, 50134, Florence, Italy.
Maura CalvaniDepartment of Experimental and Clinical Biomedical Sciences, University of Florence, 50134, Florence, Italy.
Francesca BianchiniDepartment of Experimental and Clinical Biomedical Sciences, University of Florence, 50134, Florence, Italy.
Barbara RichichiDepartment of Chemistry, University of Florence, 50019, Sesto Fiorentino, Italy.
Giovanni RaugeiDepartment of Experimental and Clinical Biomedical Sciences, University of Florence, 50134, Florence, Italy.
Nicholas WongDivision of Nephrology, Department of Medicine, McMaster University, L8N4A6, Hamilton, Ontario, Canada.
Damu TangDivision of Nephrology, Department of Medicine, McMaster University, L8N4A6, Hamilton, Ontario, Canada.
Paola ChiarugiDepartment of Experimental and Clinical Biomedical Sciences, University of Florence, 50134, Florence, Italy.
University of Florence · ITMcMaster University · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cancer associated fibroblasts (CAFs) are key determinants of cancer progression. In prostate carcinoma (PCa), CAFs induce epithelial-mesenchymal transition (EMT) and metabolic reprogramming of PCa cells towards oxidative phosphorylation (OXPHOS), promoting tumor growth and metastatic dissemination. We herein establish a novel role for pyruvate kinase M2 (PKM2), an established effector of Warburg-like glycolytic behavior, in OXPHOS metabolism induced by CAFs. Indeed, CAFs promote PKM2 post-translational modifications, such as cysteine oxidation and Src-dependent tyrosine phosphorylation, allowing nuclear migration of PKM2 and the formation of a trimeric complex with hypoxia inducible factor-1α (HIF-1α) and the transcriptional repressor Differentially Expressed in Chondrocytes-1 (DEC1). DEC1 recruitment is mandatory for downregulating miR205 expression, thereby fostering EMT execution and metabolic switch toward OXPHOS. Furthermore, the analysis of a cohort of PCa patients reveals a significant positive correlation between PKM2 nuclear localization and cancer aggressiveness, thereby validating our in vitro observations. Crucially, in vitro and in vivo pharmacological targeting of PKM2 nuclear translocation using DASA-58, as well as metformin, impairs metastatic dissemination of PCa cells in SCID mice. Our study indicates that impairing the metabolic tumor:stroma interplay by targeting the PKM2/OXPHOS axis, may be a valuable novel therapeutic approach in aggressive prostate carcinoma.

Indexed as

Active Transport, Cell NucleusAnimalsBinding SitesCarcinomaCarrier ProteinsCell Line, TumorCell NucleusCohort StudiesCysteineFibroblastsGlucoseHumansHypoxia-Inducible Factor 1, alpha SubunitImmunohistochemistryLactic AcidMaleCarrier ProteinsCysteineDELEC1 protein, humanGlucoseHIF1A protein, humanHypoxia-Inducible Factor 1, alpha SubunitLactic AcidMembrane ProteinsMetforminMicroRNAsMIR205, humanOxygenPyruvate KinaseThyroid Hormone-Binding ProteinsThyroid HormonesTumor Suppressor Proteinscancer associated fibroblastsepithelial-mesenchymal transitionhypoxia inducible factor-1αprostate cancerpyruvate kinase M2

Identifiers

PMID26183399
PMCPMC4695170
OpenAlexW1952270399

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.