Evidence map›Paper›PMID 33579235›Full record

ArticleBMC cancer2021

ERK3 is transcriptionally upregulated by ∆Np63α and mediates the role of ∆Np63α in suppressing cell migration in non-melanoma skin cancers.

Eid S Alshammari, Amjad A Aljagthmi, Andrew J Stacy, Mike Bottomley, H Nicholas Shamma, Madhavi P Kadakia, Weiwen Long

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.3field-weighted citation impact, top 17% 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

9 citing papers in PubMed, 16 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Frontiers in cell and developmental biology · 2022
    Review
  8. Article
  9. Proceedings of the National Academy of Sciences of the United States of America · 2021
    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

7 authors at 1 institution in 2 countries.

Eid S Alshammari *Department of Biochemistry and Molecular Biology, Boonshoft School of Medicine, Wright State University, 112 Diggs Laboratory, 3640 Colonel Glenn Highway, Dayton, OH, 45435, USA.
Amjad A Aljagthmi *Department of Biochemistry and Molecular Biology, Boonshoft School of Medicine, Wright State University, 112 Diggs Laboratory, 3640 Colonel Glenn Highway, Dayton, OH, 45435, USA.
Andrew J StacyDepartment of Biochemistry and Molecular Biology, Boonshoft School of Medicine, Wright State University, 112 Diggs Laboratory, 3640 Colonel Glenn Highway, Dayton, OH, 45435, USA.
Mike BottomleyDepartment of Math and Microbiology, College of Science and Mathematics, Wright State University, Dayton, OH, 45435, USA.
H Nicholas ShammaDepartment of Dermatology, Boonshoft School of Medicine, Wright State University, 3640 Colonel Glenn Highway, Dayton, OH, 45435, USA.
Madhavi P KadakiaDepartment of Biochemistry and Molecular Biology, Boonshoft School of Medicine, Wright State University, 112 Diggs Laboratory, 3640 Colonel Glenn Highway, Dayton, OH, 45435, USA. madhavi.kadakia@wright.edu.
Weiwen LongDepartment of Biochemistry and Molecular Biology, Boonshoft School of Medicine, Wright State University, 112 Diggs Laboratory, 3640 Colonel Glenn Highway, Dayton, OH, 45435, USA. weiwen.long@wright.edu.
Wright State University · US

Funding

ERK3 Kinase Signaling in Lung CancerR01CA193264 · NCI · WRIGHT STATE UNIVERSITY · PI LONG, WEIWEN · 2015 to 2019
$1.7M
Role of DeltaNp63alpha in Vitamin D Mediated Cell Survival in Skin CancerR01CA154715 · NCI · WRIGHT STATE UNIVERSITY · PI KADAKIA, MADHAVI P · 2012 to 2016
$1.4M
NCI NIH HHS 1R01CA154715NCI NIH HHS 5R01CA193264NCI NIH HHS R01 CA154715NCI NIH HHS R01 CA193264
6 · The paper itself

Abstract

backgroundp63, a member of the p53 gene family, is an important regulator for epithelial tissue growth and development. ∆Np63α is the main isoform of p63 and highly expressed in Non-melanoma skin cancer (NMSC). Extracellular signal-regulated kinase 3 (ERK3) is an atypical mitogen-activated protein kinase (MAPK) whose biochemical features and cellular regulation are distinct from those of conventional MAPKs such as ERK1/2. While ERK3 has been shown to be upregulated in lung cancers and head and neck cancers, in which it promotes cancer cell migration and invasion, little is known about the implication of ERK3 in NMSCs.

methodsFluorescent immunohistochemistry was performed to evaluate the expression levels of ΔNp63α and ERK3 in normal and NMSC specimens. Dunnett's test was performed to compare mean fluorescence intensity (MFI, indicator of expression levels) of p63 or ERK3 between normal cutaneous samples and NMSC samples. A mixed effects (ANOVA) test was used to determine the correlation between ΔNp63α and ERK3 expression levels (MFI). The regulation of ERK3 by ΔNp63α was studied by qRT-PCR, Western blot and luciferase assay. The effect of ERK3 regulation by ΔNp63α on cell migration was measured by performing trans-well migration assay.

resultsThe expression level of ∆Np63α is upregulated in NMSCs compared to normal tissue. ERK3 level is significantly upregulated in AK and SCC in comparison to normal tissue and there is a strong positive correlation between ∆Np63α and ERK3 expression in normal skin and skin specimens of patients with AK, SCC or BCC. Further, we found that ∆Np63α positively regulates ERK3 transcript and protein levels in A431 and HaCaT skin cells, underlying the upregulation of ERK3 expression and its positive correlation with ∆Np63α in NMSCs. Moreover, similar to the effect of ∆Np63α depletion, silencing ERK3 greatly enhanced A431 cell migration. Restoration of ERK3 expression under the condition of silencing ∆Np63α counteracted the increase in cell migration induced by the depletion of ∆Np63α. Mechanistically, ERK3 inhibits the phosphorylation of Rac1 G-protein and the formation of filopodia of A431 skin SCC cells.

conclusionsERK3 is positively regulated by ∆Np63α and mediates the role of ∆Np63α in suppressing cell migration in NMSC.

Indexed as

Cell MovementGene Expression Regulation, NeoplasticTranscriptional ActivationCell LineCell Line, TumorHumansMitogen-Activated Protein Kinase 6Phosphorylationrac1 GTP-Binding ProteinSkin NeoplasmsTranscription FactorsTumor Suppressor ProteinsMitogen-Activated Protein Kinase 6rac1 GTP-Binding ProteinRAC1 protein, humanTP63 protein, humanTranscription FactorsTumor Suppressor ProteinsERK3IHCMigrationNMSCSCCΔNp63α

Identifiers

PMID33579235
PMCPMC7881562
OpenAlexW3128176156

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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.