Evidence map›Paper›PMID 25341034›Full record

ArticleCell death & disease2014

RAGE is essential for oncogenic KRAS-mediated hypoxic signaling in pancreatic cancer.

R Kang, W Hou, Q Zhang, R Chen, Y J Lee, D L Bartlett, M T Lotze, D Tang, H J Zeh

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

Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed, 2 pooled it
3.8field-weighted citation impact, top 6% 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

59 citing papers in PubMed, 2 syntheses or guidelines pooled it, 90 citations in OpenAlex.

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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

9 authors at 1 institution in 1 country.

R KangDivision of Gastrointestinal Surgical Oncology, Department of Surgery, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA 15219, USA.
W HouDivision of Gastrointestinal Surgical Oncology, Department of Surgery, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA 15219, USA.
Q ZhangDivision of Gastrointestinal Surgical Oncology, Department of Surgery, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA 15219, USA.
R ChenDivision of Gastrointestinal Surgical Oncology, Department of Surgery, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA 15219, USA.
Y J LeeDivision of Gastrointestinal Surgical Oncology, Department of Surgery, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA 15219, USA.
D L BartlettDivision of Gastrointestinal Surgical Oncology, Department of Surgery, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA 15219, USA.
M T LotzeDivision of Gastrointestinal Surgical Oncology, Department of Surgery, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA 15219, USA.
D TangDivision of Gastrointestinal Surgical Oncology, Department of Surgery, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA 15219, USA.
H J ZehDivision of Gastrointestinal Surgical Oncology, Department of Surgery, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA 15219, USA.
UPMC Hillman Cancer Center · US

Funding

VECTOR CORE FACILITYP30CA047904 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Leonard J. Appleman · 1988 to 2026
$158.0M
Targeting HMGB1-mediated Autophagy in Cancer TherapyR01CA160417 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI TANG, DAOLIN · 2012 to 2023
$3.0M
Multimodality approach to hepatic colorectal metastasesR01CA140554 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BARTLETT, DAVID L, LEE, YONG J · 2010 to 2014
$1.6M
Pancreatic Ductal Adenocarcinoma is a disease of constitutive autophagyR01CA181450 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LOTZE, MICHAEL T, ZEH, HERBERT J · 2014 to 2018
$1.6M
NCI NIH HHS P30 CA047904NCI NIH HHS P30CA047904NCI NIH HHS R01 CA140554NCI NIH HHS R01CA140554NCI NIH HHS R01 CA160417NCI NIH HHS R01CA160417NCI NIH HHS R01 CA181450NCI NIH HHS R01CA181450
6 · The paper itself

Abstract

A hypoxic tumor microenvironment is characteristic of many cancer types, including one of the most lethal, pancreatic cancer. We recently demonstrated that the receptor for advanced glycation end products (RAGE) has an important role in promoting the development of pancreatic cancer and attenuating the response to chemotherapy. We now demonstrate that binding of RAGE to oncogenic KRAS facilitates hypoxia-inducible factor 1 (HIF1)α activation and promotes pancreatic tumor growth under hypoxic conditions. Hypoxia induces NF-κB-dependent and HIF1α-independent RAGE expression in pancreatic tumor cells. Moreover, the interaction between RAGE and mutant KRAS increases under hypoxia, which in turn sustains KRAS signaling pathways (RAF-MEK-ERK and PI3K-AKT), facilitating stabilization and transcriptional activity of HIF1α. Knock down of RAGE in vitro inhibits KRAS signaling, promotes HIF1α degradation, and increases hypoxia-induced pancreatic tumor cell death. RAGE-deficient mice have impaired oncogenic KRAS-driven pancreatic tumor growth with significant downregulation of the HIF1α signaling pathway. Our results provide a novel mechanistic link between NF-κB, KRAS, and HIF1α, three potent molecular pathways in the cellular response to hypoxia during pancreatic tumor development and suggest alternatives for preventive and therapeutic strategies.

Indexed as

OncogenesSignal TransductionAnimalsAutophagyCell HypoxiaCell Line, TumorCell SurvivalHumansHypoxia-Inducible Factor 1, alpha SubunitMice, Inbred C57BLMice, TransgenicModels, BiologicalNF-kappa BPancreatic NeoplasmsProtein StabilityProto-Oncogene ProteinsHras protein, mouseHypoxia-Inducible Factor 1, alpha SubunitKRAS protein, humanNF-kappa BProto-Oncogene ProteinsProto-Oncogene Proteins p21(ras)ras ProteinsReceptor for Advanced Glycation End ProductsReceptors, Immunologic

Identifiers

PMID25341034
PMCPMC4237264
OpenAlexW1983520710

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.