Evidence map›Paper›PMID 26240283›Full record

ArticleMolecular and cellular biology2015

Differential Effects of Hepatocyte Nuclear Factor 4α Isoforms on Tumor Growth and T-Cell Factor 4/AP-1 Interactions in Human Colorectal Cancer Cells.

Linh M Vuong, Karthikeyani Chellappa, Joseph M Dhahbi, Jonathan R Deans, Bin Fang, Eugene Bolotin, Nina V Titova, Nate P Hoverter, Stephen R Spindler, Marian L Waterman and 1 more

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

Article in Molecular and cellular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
2.4field-weighted citation impact, top 11% 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

42 citing papers in PubMed, 67 citations in OpenAlex.

  1. The role of HNF4α in adenocarcinoma.Biochemical Society transactions · 2026
    Review
  2. Article
  3. Article
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  5. Hepatocyte Nuclear Factor 4 Alpha: A Key Regulator of Liver Disease Pathology and Haemostatic Disorders.Liver international : official journal of the International Association for the Study of the Liver · 2025
    Review
  6. Review
  7. Major roles of the circadian clock in cancer.Cancer biology & medicine · 2023
    Review
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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

11 authors at 2 institutions in 1 country.

Linh M VuongDepartment of Cell Biology and Neuroscience, University of California, Riverside, Riverside, California, USA.
Karthikeyani ChellappaDepartment of Cell Biology and Neuroscience, University of California, Riverside, Riverside, California, USA.
Joseph M DhahbiDepartment of Biochemistry, University of California, Riverside, Riverside, California, USA.
Jonathan R DeansDepartment of Cell Biology and Neuroscience, University of California, Riverside, Riverside, California, USA.
Bin FangDepartment of Cell Biology and Neuroscience, University of California, Riverside, Riverside, California, USA.
Eugene BolotinDepartment of Cell Biology and Neuroscience, University of California, Riverside, Riverside, California, USA.
Nina V TitovaDepartment of Cell Biology and Neuroscience, University of California, Riverside, Riverside, California, USA.
Nate P HoverterDepartment of Microbiology and Molecular Genetics, University of California, Irvine, Irvine, California, USA.
Stephen R SpindlerDepartment of Biochemistry, University of California, Riverside, Riverside, California, USA.
Marian L WatermanDepartment of Microbiology and Molecular Genetics, University of California, Irvine, Irvine, California, USA.
Frances M SladekDepartment of Cell Biology and Neuroscience, University of California, Riverside, Riverside, California, USA frances.sladek@ucr.edu.
University of California, Riverside · USUniversity of California, Irvine · US

Funding

Univ.of Calif., Irvine Cancer Center Support GrantP30CA062203 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI Christine Hui · 1994 to 2026
$57.9M
REGULATION OF LIVER SPECIFIC GENE EXPRESSIONR01DK053892 · NIDDK · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI SLADEK, FRANCES M. · 1998 to 2015
$5.3M
LEF/TCF Expression in Colon CancerR01CA096878 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI WATERMAN, MARIAN L · 2003 to 2012
$2.7M
Wnt Signaling in Colon CancerR01CA108697 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI WATERMAN, MARIAN L · 2005 to 2015
$2.7M
Nuclear Receptor DNA Binding in Human Physiology and DiseaseR01DK094707 · NIDDK · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI SLADEK, FRANCES M. · 2012 to 2015
$1.5M
Regulation of Liver-Specific Gene ExpressionR56DK053892 · NIDDK · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI SLADEK, FRANCES M · 2007 to 2007
$436k
The Role of HNF4alpha in Cell ProliferationF31HD068611 · NICHD · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI VUONG, LINH · 2010 to 2013
$99k
NCI NIH HHS CA096878NCI NIH HHS CA108697NCI NIH HHS P30 CA062203NCI NIH HHS R01 CA096878NCI NIH HHS R01 CA108697NICHD NIH HHS F31 HD068611NIDDK NIH HHS DK053892NIDDK NIH HHS DK094707NIDDK NIH HHS R01 DK053892NIDDK NIH HHS R01 DK094707NIDDK NIH HHS R56 DK053892
6 · The paper itself

Abstract

The nuclear receptor hepatocyte nuclear factor 4α (HNF4α) is tumor suppressive in the liver but amplified in colon cancer, suggesting that it also might be oncogenic. To investigate whether this discrepancy is due to different HNF4α isoforms derived from its two promoters (P1 and P2), we generated Tet-On-inducible human colon cancer (HCT116) cell lines that express either the P1-driven (HNF4α2) or P2-driven (HNF4α8) isoform and analyzed them for tumor growth and global changes in gene expression (transcriptome sequencing [RNA-seq] and chromatin immunoprecipitation sequencing [ChIP-seq]). The results show that while HNF4α2 acts as a tumor suppressor in the HCT116 tumor xenograft model, HNF4α8 does not. Each isoform regulates the expression of distinct sets of genes and recruits, colocalizes, and competes in a distinct fashion with the Wnt/β-catenin mediator T-cell factor 4 (TCF4) at CTTTG motifs as well as at AP-1 motifs (TGAXTCA). Protein binding microarrays (PBMs) show that HNF4α and TCF4 share some but not all binding motifs and that single nucleotide polymorphisms (SNPs) in sites bound by both HNF4α and TCF4 can alter binding affinity in vitro, suggesting that they could play a role in cancer susceptibility in vivo. Thus, the HNF4α isoforms play distinct roles in colon cancer, which could be due to differential interactions with the Wnt/β-catenin/TCF4 and AP-1 pathways.

Indexed as

AnimalsBase SequenceBinding, CompetitiveColorectal NeoplasmsConsensus SequenceGene Expression Regulation, NeoplasticGene OntologyHCT116 CellsHepatocyte Nuclear Factor 1-alphaHepatocyte Nuclear Factor 4HumansMaleMice, NudeNeoplasm TransplantationPolymorphism, Single NucleotideProtein BindingHepatocyte Nuclear Factor 1-alphaHepatocyte Nuclear Factor 4HNF1A protein, humanHNF4A protein, humanProtein IsoformsTranscription Factor AP-1

Identifiers

PMID26240283
PMCPMC4573706
OpenAlexW2208387402

What OpenQuestion holds

Textmetadata
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.