Evidence map›Paper›PMID 22493428›Full record

ArticleThe Journal of biological chemistry2012

Nanog increases focal adhesion kinase (FAK) promoter activity and expression and directly binds to FAK protein to be phosphorylated.

Baotran Ho, Gretchen Olson, Sheila Figel, Irwin Gelman, William G Cance, Vita M Golubovskaya

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
4.0field-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

39 citing papers in PubMed, 75 citations in OpenAlex.

  1. Article
  2. Article
  3. Self-transfecting GMO-PMO chimera targetingMolecular therapy. Nucleic acids · 2023
    Article
  4. Article
  5. FAK in Cancer: From Mechanisms to Therapeutic Strategies.International journal of molecular sciences · 2022
    Review
  6. Review
  7. Genetic variations in theExperimental and therapeutic medicine · 2021
    Article
  8. Review
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  10. Article
  11. Article
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  14. Article
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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 2 institutions in 1 country.

Baotran HoDepartment of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
Gretchen Olson
Sheila Figel
Irwin Gelman
William G Cance
Vita M Golubovskaya
Cancer Genetics (United States) · USRoswell Park Comprehensive Cancer Center · US

Funding

Two-Spirit Films in Indigenous Cancer HealthP30CA016056 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI MARK G FRATTINI · 1985 to 2026
$116.6M
FOCAL ADHESION KINASE--TUMOR BIOLOGY AND THERAPEUTICSR01CA065910 · NCI · UNIVERSITY OF NORTH CAROLINA CHAPEL HILL · PI MARLOWE, TIMOTHY A · 1996 to 2019
$6.3M
Focal Adhesion Kinase - Tumor Biology and TherapeuticsR37CA065910 · NCI · UNIVERSITY OF ARIZONA · PI Timothy A Marlowe · 2022 to 2026
$1.6M
NCI NIH HHS CA65910NCI NIH HHS P30 CA016056NCI NIH HHS R01 CA065910NCI NIH HHS R37 CA065910
6 · The paper itself

Abstract

Nanog and FAK were shown to be overexpressed in cancer cells. In this report, the Nanog overexpression increased FAK expression in 293, SW480, and SW620 cancer cells. Nanog binds the FAK promoter and up-regulates its activity, whereas Nanog siRNA decreases FAK promoter activity and FAK mRNA. The FAK promoter contains four Nanog-binding sites. The site-directed mutagenesis of these sites significantly decreased up-regulation of FAK promoter activity by Nanog. EMSA showed the specific binding of Nanog to each of the four sites, and binding was confirmed by ChIP assay. Nanog directly binds the FAK protein by pulldown and immunoprecipitation assays, and proteins co-localize by confocal microscopy. Nanog binds the N-terminal domain of FAK. In addition, FAK directly phosphorylates Nanog in a dose-dependent manner by in vitro kinase assay and in cancer cells in vivo. The site-directed mutagenesis of Nanog tyrosines, Y35F and Y174F, blocked phosphorylation and binding by FAK. Moreover, overexpression of wild type Nanog increased filopodia/lamellipodia formation, whereas mutant Y35F and Y174F Nanog did not. The wild type Nanog increased cell invasion that was inhibited by the FAK inhibitor and increased by FAK more significantly than with the mutants Y35F and Y174F Nanog. Down-regulation of Nanog with siRNA decreased cell growth reversed by FAK overexpression. Thus, these data demonstrate the regulation of the FAK promoter by Nanog, the direct binding of the proteins, the phosphorylation of Nanog by FAK, and the effect of FAK and Nanog cross-regulation on cancer cell morphology, invasion, and growth that plays a significant role in carcinogenesis.

Indexed as

Promoter Regions, GeneticBase SequenceCell LineFocal Adhesion Protein-Tyrosine KinasesHomeodomain ProteinsHumansMolecular Sequence DataMutagenesis, Site-DirectedNanog Homeobox ProteinPhosphorylationProtein BindingFocal Adhesion Protein-Tyrosine KinasesHomeodomain ProteinsNanog Homeobox ProteinNANOG protein, human

Identifiers

PMID22493428
PMCPMC3365765
OpenAlexW1981986780

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.