Evidence map›Paper›PMID 27197190›Full record

ArticleCancer research2016

A Novel MIF Signaling Pathway Drives the Malignant Character of Pancreatic Cancer by Targeting NR3C2.

Shouhui Yang, Peijun He, Jian Wang, Aaron Schetter, Wei Tang, Naotake Funamizu, Katsuhiko Yanaga, Tadashi Uwagawa, Abhay R Satoskar, Jochen Gaedcke and 9 more

Open access · greenAbstract read
In one paragraph

Article in Cancer research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 220 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
220citing papers in PubMed, 1 pooled it
8.4field-weighted citation impact, top 2% 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

220 citing papers in PubMed, 1 synthesis or guideline pooled it, 409 citations in OpenAlex.

  1. Pooled it
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160 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

19 authors at 1 institution in 1 country.

Shouhui YangPancreatic Cancer Unit, National Cancer Institute, Bethesda, Maryland. Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.
Peijun HePancreatic Cancer Unit, National Cancer Institute, Bethesda, Maryland. Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.
Jian WangPancreatic Cancer Unit, National Cancer Institute, Bethesda, Maryland. Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.
Aaron SchetterLaboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.
Wei TangLaboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.
Naotake FunamizuDepartment of Surgery, Jikei University School of Medicine, Tokyo, Japan.
Katsuhiko YanagaDepartment of Surgery, Jikei University School of Medicine, Tokyo, Japan.
Tadashi UwagawaDepartment of Surgery, Jikei University School of Medicine, Tokyo, Japan.
Abhay R SatoskarDepartment Pathology and Microbiology, Ohio State University, Columbus, Ohio.
Jochen GaedckeDepartment of General, Visceral and Pediatric Surgery, University Medicine, Göttingen, Germany.
Markus BernhardtDepartment of General, Visceral and Pediatric Surgery, University Medicine, Göttingen, Germany.
B Michael GhadimiDepartment of General, Visceral and Pediatric Surgery, University Medicine, Göttingen, Germany.
Matthias M GaidaInstitute of Pathology, University of Heidelberg, Heidelberg, Germany.
Frank BergmannInstitute of Pathology, University of Heidelberg, Heidelberg, Germany.
Jens WernerDepartment of Surgery, Ludwig-Maximillians University, Munich, Germany.
Thomas RiedGenetics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.
Nader HannaDivision of Surgical Oncology, University of Maryland School of Medicine, Baltimore, Maryland.
H Richard AlexanderDivision of Surgical Oncology, University of Maryland School of Medicine, Baltimore, Maryland.
S Perwez HussainPancreatic Cancer Unit, National Cancer Institute, Bethesda, Maryland. Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland. hussainp@mail.nih.gov.
Jikei University School of Medicine · JP

Funding

Molecular Profiling of Pancreatic CancerZIABC011162 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI HUSSAIN, SYED PERWEZ · 2009 to 2023
$11.1M
Role of Inflammation in the Development and Progression of Pancreatic CancerZIABC011185 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI HUSSAIN, SYED PERWEZ · 2009 to 2023
$10.4M
Intramural NIH HHS Z99 CA999999Intramural NIH HHS ZIA BC011162
6 · The paper itself

Abstract

Pancreatic cancers with aberrant expression of macrophage migration inhibitory factor (MIF) are particularly aggressive. To identify key signaling pathways that drive disease aggressiveness in tumors with high MIF expression, we analyzed the expression of coding and noncoding genes in high and low MIF-expressing tumors in multiple cohorts of pancreatic ductal adenocarcinoma (PDAC) patients. The key genes and pathways identified were linked to patient survival and were mechanistically, functionally, and clinically characterized using cell lines, a genetically engineered mouse model, and PDAC patient cohorts. Here, we report evidence of a novel MIF-driven signaling pathway that inhibits the orphan nuclear receptor NR3C2, a previously undescribed tumor suppressor that impacts aggressiveness and survival in PDAC. Mechanistically, MIF upregulated miR-301b that targeted NR3C2 and suppressed its expression. PDAC tumors expressing high levels of MIF displayed elevated levels of miR-301b and reduced levels of NR3C2. In addition, reduced levels of NR3C2 expression correlated with poorer survival in multiple independent cohorts of PDAC patients. Functional analysis showed that NR3C2 inhibited epithelial-to-mesenchymal transition and enhanced sensitivity to the gemcitabine, a chemotherapeutic drug used in PDAC standard of care. Furthermore, genetic deletion of MIF disrupted a MIF-mir-301b-NR3C2 signaling axis, reducing metastasis and prolonging survival in a genetically engineered mouse model of PDAC. Taken together, our results offer a preclinical proof of principle for candidate therapies to target a newly described MIF-miR-301b-NR3C2 signaling axis for PDAC management. Cancer Res; 76(13); 3838-50. ©2016 AACR.

Indexed as

AnimalsAntimetabolites, AntineoplasticApoptosisBiomarkers, TumorCarcinoma, Pancreatic DuctalCell MovementCell ProliferationDeoxycytidineEpithelial-Mesenchymal TransitionGemcitabineGene Expression Regulation, NeoplasticHumansIntramolecular OxidoreductasesMacrophage Migration-Inhibitory FactorsMiceMice, KnockoutAntimetabolites, AntineoplasticBiomarkers, TumorDeoxycytidineGemcitabineIntramolecular OxidoreductasesMacrophage Migration-Inhibitory FactorsMicroRNAsMIF protein, humanNR3C2 protein, humanReceptors, Mineralocorticoid

Identifiers

PMID27197190
PMCPMC4930741
OpenAlexW2336715782

What OpenQuestion holds

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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.