Evidence map›Paper›PMID 26124282›Full record

ArticleMolecular and cellular biology2015

Phosphatidic Acid Increases Epidermal Growth Factor Receptor Expression by Stabilizing mRNA Decay and by Inhibiting Lysosomal and Proteasomal Degradation of the Internalized Receptor.

Nathaniel Hatton, Erin Lintz, Madhu Mahankali, Karen M Henkels, Julian Gomez-Cambronero

Open access · bronzeAbstract read
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 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

16 citing papers in PubMed, 30 citations in OpenAlex.

  1. Article
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  5. D-series Resolvins activate Phospholipase D in phagocytes during inflammation and resolution.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020
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  16. Molecular Pathways: Targeting Diacylglycerol Kinase Alpha in Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2015
    Article
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

5 authors at 1 institution in 1 country.

Nathaniel HattonDepartment of Biochemistry and Molecular Biology, Wright State University School of Medicine, Dayton, Ohio, USA.
Erin LintzDepartment of Biochemistry and Molecular Biology, Wright State University School of Medicine, Dayton, Ohio, USA.
Madhu MahankaliDepartment of Biochemistry and Molecular Biology, Wright State University School of Medicine, Dayton, Ohio, USA.
Karen M HenkelsDepartment of Biochemistry and Molecular Biology, Wright State University School of Medicine, Dayton, Ohio, USA.
Julian Gomez-CambroneroDepartment of Biochemistry and Molecular Biology, Wright State University School of Medicine, Dayton, Ohio, USA julian.cambronero@wright.edu.ORCID http://orcid.org/0000-0002-7581-9227
Wright State University · US

Funding

PLD2, as a GEF or as a Lipase, is Central to Leukocyte ChemotaxisR01HL056653 · NHLBI · WRIGHT STATE UNIVERSITY · PI CAMBRONERO, JULIAN G. · 2004 to 2016
$4.0M
NHLBI NIH HHS HL05665314NHLBI NIH HHS R01 HL056653
6 · The paper itself

Abstract

Overexpression of epidermal growth factor receptor (EGFR) is one of the frequent mechanisms implicated in cancer progression, and so is the overexpression of the enzyme phospholipase D (PLD) and its reaction product, phosphatidic acid (PA). However, an understanding of how these signaling molecules interact at the level of gene expression is lacking. Catalytically active PLD enhanced expression of EGFR in human breast cancer cells. Overexpression of the PLD2 isoform increased EGFR mRNA and protein expression. It also negated an EGFR downregulation mediated by small interfering RNA targeting EGFR (siEGFR). Several mechanisms contributed to the alteration in EGFR expression. First was the stabilization of EGFR transcripts as PLD2 delayed mRNA decay, which prolonged their half-lives. Second, RNase enzymatic activity was inhibited by PA. Third, protein stabilization also occurred, as indicated by PLD resistance to cycloheximide-induced EGFR protein degradation. Fourth, PA inhibited lysosomal and proteasomal degradation of internalized EGFR. PLD2 and EGFR colocalized at the cell membrane, and JAK3 phosphorylation at Tyr980/Tyr981 followed receptor endocytosis. Further, the presence of PLD2 increased stabilization of intracellular EGFR in large recycling vesicles at ∼15 min of EGF stimulation. Thus, PLD2-mediated production of PA contributed to the control of EGFR exposure to ligand through a multipronged transcriptional and posttranscriptional program during the out-of-control accumulation of EGFR signaling in cancer cells.

Indexed as

AnimalsBreast NeoplasmsCell Line, TumorChlorocebus aethiopsCOS CellsCycloheximideEndocytosisErbB ReceptorsFemaleHumansJanus Kinase 3LysosomesMCF-7 CellsPhosphatidic AcidsPhospholipase DProteasome Endopeptidase ComplexCycloheximideErbB ReceptorsJAK3 protein, humanJanus Kinase 3Phosphatidic AcidsPhospholipase DProteasome Endopeptidase ComplexRibonucleasesRNA, MessengerRNA, Small Interfering

Identifiers

PMID26124282
PMCPMC4539377
OpenAlexW2115545903

What Socratic 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 Socratic graph.