Evidence map›Paper›PMID 23318458›Full record

ArticleOncogene2014

The HMGB1/RAGE inflammatory pathway promotes pancreatic tumor growth by regulating mitochondrial bioenergetics.

R Kang, D Tang, N E Schapiro, T Loux, K M Livesey, T R Billiar, H Wang, B Van Houten, M T Lotze, H J Zeh

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncogene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 138 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
138citing papers in PubMed, 5 pooled it
14.3field-weighted citation impact, top 1% 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

138 citing papers in PubMed, 5 syntheses or guidelines pooled it, 231 citations in OpenAlex.

  1. Pooled it
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  8. HMGB1: A Central Node in Cancer Therapy Resistance.International journal of molecular sciences · 2025
    Review
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78 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

10 authors at 3 institutions in 1 country.

R KangDepartment of Surgery, Hillman Cancer Center, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
D TangDepartment of Surgery, Hillman Cancer Center, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
N E SchapiroDepartment of Surgery, Hillman Cancer Center, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
T LouxDepartment of Surgery, Hillman Cancer Center, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
K M LiveseyDepartment of Surgery, Hillman Cancer Center, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
T R BilliarDepartment of Surgery, Hillman Cancer Center, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
H WangNorth Shore University Hospital, New York University School of Medicine, Manhasset, NY, USA.
B Van HoutenLaboratory of Molecular and Cell Biology Program, Hillman Cancer Center, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA, USA.
M T LotzeDepartment of Surgery, Hillman Cancer Center, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
H J ZehDepartment of Surgery, Hillman Cancer Center, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
UPMC Hillman Cancer Center · USUniversity of Pittsburgh · USNew York University · US

Funding

VECTOR CORE FACILITYP30CA047904 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Jessie Nedrow · 1988 to 2026
$158.0M
PROTEOMICS COREP01CA101944 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LOTZE, MICHAEL T · 2005 to 2009
$8.5M
Targeting HMGB1-mediated Autophagy in Cancer TherapyR01CA160417 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI TANG, DAOLIN · 2012 to 2023
$3.0M
NCI NIH HHS P01 CA 101944NCI NIH HHS P01 CA101944NCI NIH HHS P30 CA047904NCI NIH HHS P30CA047904NCI NIH HHS R01 CA160417NCI NIH HHS R01CA160417
6 · The paper itself

Abstract

Tumor cells require increased adenosine triphosphate (ATP) to support anabolism and proliferation. The precise mechanisms regulating this process in tumor cells are unknown. Here, we show that the receptor for advanced glycation endproducts (RAGE) and one of its primary ligands, high-mobility group box 1 (HMGB1), are required for optimal mitochondrial function within tumors. We found that RAGE is present in the mitochondria of cultured tumor cells as well as primary tumors. RAGE and HMGB1 coordinately enhanced tumor cell mitochondrial complex I activity, ATP production, tumor cell proliferation and migration. Lack of RAGE or inhibition of HMGB1 release diminished ATP production and slowed tumor growth in vitro and in vivo. These findings link, for the first time, the HMGB1-RAGE pathway with changes in bioenergetics. Moreover, our observations provide a novel mechanism within the tumor microenvironment by which necrosis and inflammation promote tumor progression.

Indexed as

Adenosine TriphosphateAnimalsButadienesCD24 AntigenCell Line, TumorCell MovementCell ProliferationCycloheximideElectron Transport Complex IEnergy MetabolismEnzyme InhibitorsExtracellular Signal-Regulated MAP KinasesHMGB1 ProteinHumansInflammationMAP Kinase Kinase 2Adenosine TriphosphateButadienesCD24 AntigenCd24a protein, mouseCycloheximideElectron Transport Complex IEnzyme InhibitorsExtracellular Signal-Regulated MAP KinasesHMGB1 ProteinHMGB1 protein, humanMap2k2 protein, mouseMAP Kinase Kinase 2NF-kappa BNitrilesProtein Synthesis InhibitorsReceptor for Advanced Glycation End ProductsRNA, Small InterferingRotenoneTlr2 protein, mouseTlr4 protein, mouseToll-Like Receptor 2Toll-Like Receptor 4U 0126Uncoupling Agents

Identifiers

PMID23318458
PMCPMC3795800
OpenAlexW2048296320

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.