Evidence map›Paper›PMID 24452790›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2014

FOXM1c promotes pancreatic cancer epithelial-to-mesenchymal transition and metastasis via upregulation of expression of the urokinase plasminogen activator system.

Chen Huang, Dacheng Xie, Jiujie Cui, Qi Li, Yong Gao, Keping Xie

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

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed
4.7field-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

60 citing papers in PubMed, 84 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

6 authors at 3 institutions in 1 country.

Chen HuangAuthors' Affiliations: Shanghai Key Laboratory of Pancreatic Diseases Research; Departments of General Surgery and Oncology, Shanghai Jiaotong University Affiliated First People's Hospital; Department of Oncology and Tumor Institute, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China; and Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Dacheng Xie
Jiujie Cui
Qi Li
Yong Gao
Keping Xie
Tongji University · CNShanghai First People's Hospital · CNShanghai East Hospital · CN

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
Targeting CDK4 in TGS-B Inactivated Gastrointestinal CancersP01CA130821 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI MISHRA, LOPA · 2008 to 2013
$6.9M
Molecular Mediators of Pancreatic Cancer Invasion and ProgressionR01CA172233 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI BRESALIER, ROBERT S · 2013 to 2017
$1.7M
Functional Validation of Pancreatic Cancer Progression BiomarkerR01CA152309 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI XIE, KEPING · 2010 to 2014
$1.6M
KLF4 Genetic and Epigenetic Changes in Human Pancreatic CancerR01CA129956 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI XIE, KEPING · 2008 to 2012
$1.3M
Genetic Approaches to Pancreatic Cancer ProgressionR01CA148954 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI XIE, KEPING · 2010 to 2014
$1.3M
NCI NIH HHS P01 CA130821NCI NIH HHS P30 CA016672NCI NIH HHS R01 CA129956NCI NIH HHS R01-CA129956NCI NIH HHS R01 CA148954NCI NIH HHS R01-CA148954NCI NIH HHS R01 CA152309NCI NIH HHS R01-CA152309NCI NIH HHS R01 CA172233NCI NIH HHS R01-CA172233
6 · The paper itself

Abstract

purposeThe transcription factor Forkhead box M1 (FOXM1) plays important roles in the formation of several human tumors, including pancreatic cancer. However, the molecular mechanisms by which FOXM1 promotes pancreatic tumor epithelial-to-mesenchymal transition (EMT) and metastasis are unknown. EXPERIMENTAL

designThe effect of altered expression of FOXM1 and urokinase-type plasminogen activator receptor (uPAR) on EMT and metastasis was examined using animal models of pancreatic cancer. Also, the underlying mechanisms of altered pancreatic cancer invasion and metastasis were analyzed using in vitro molecular biology assays. Finally, the clinical relevance of dysregulated FOXM1/uPAR signaling was investigated using pancreatic tumor and normal pancreatic tissue specimens.

resultsPancreatic tumor specimens and cell lines predominantly overexpressed the FOXM1 isoform FOXM1c. FOXM1c overexpression promoted EMT in and migration, invasion, and metastasis of pancreatic cancer cells, whereas downregulation of FOXM1 expression inhibited these processes. The level of FOXM1 expression correlated directly with that of uPAR expression in pancreatic cancer cell lines and tumor specimens. Moreover, FOXM1c overexpression upregulated uPAR expression in pancreatic cancer cells, whereas inhibition of FOXM1 expression suppressed uPAR expression. Furthermore, transfection of FOXM1c into pancreatic cancer cells directly activated the uPAR promoter, whereas inhibition of FOXM1 expression by FOXM1 siRNA suppressed its activation in these cells. Finally, we identified an FOXM1-binding site in the uPAR promoter and demonstrated that FOXM1 protein bound directly to it. Deletion mutation of this site significantly attenuated uPAR promoter activity.

conclusionsOur findings demonstrated that FOXM1c contributes to pancreatic cancer development and progression by enhancing uPAR gene transcription, and thus, tumor EMT and metastasis.

Indexed as

AdenocarcinomaAnimalsChromatin ImmunoprecipitationEpithelial-Mesenchymal TransitionForkhead Box Protein M1Forkhead Transcription FactorsHumansImmunohistochemistryNeoplasm InvasivenessNeoplasm MetastasisPancreatic NeoplasmsReal-Time Polymerase Chain ReactionReceptors, Urokinase Plasminogen ActivatorReverse Transcriptase Polymerase Chain ReactionRNA, Small InterferingSignal TransductionForkhead Box Protein M1Forkhead Transcription FactorsFOXM1 protein, humanReceptors, Urokinase Plasminogen ActivatorRNA, Small Interfering

Identifiers

PMID24452790
PMCPMC3959252
OpenAlexW2158089750

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.