Evidence map›Paper›PMID 32816038›Full record

ArticleCarcinogenesis2021

Targeting 14-3-3ε activates apoptotic signaling to prevent cutaneous squamous cell carcinoma.

Thomas R Holmes, Jenan Al Matouq, Matti Holmes, Natasha Sioda, Justin C Rudd, Celia Bloom, Lauren Nicola, Nicholas Y Palermo, Justin G Madson, Sándor Lovas and 1 more

Open access · greenAbstract read
In one paragraph

Article in Carcinogenesis, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
0.5field-weighted citation impact, top 37% 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

12 citing papers in PubMed, 19 citations in OpenAlex.

  1. Article
  2. The human Flower isoform hFWE4 facilitates cornification in cutaneous squamous cell carcinoma.JID innovations : skin science from molecules to population health · 2026
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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 3 institutions in 1 country.

Thomas R HolmesDepartment of Biomedical Sciences, Creighton University School of Medicine, Omaha, NE, USA.
Jenan Al MatouqDepartment of Biomedical Sciences, Creighton University School of Medicine, Omaha, NE, USA.
Matti HolmesDepartment of Biomedical Sciences, Creighton University School of Medicine, Omaha, NE, USA.
Natasha SiodaDepartment of Biomedical Sciences, Creighton University School of Medicine, Omaha, NE, USA.
Justin C RuddDepartment of Biomedical Sciences, Creighton University School of Medicine, Omaha, NE, USA.
Celia BloomDepartment of Biomedical Sciences, Creighton University School of Medicine, Omaha, NE, USA.
Lauren NicolaDepartment of Biomedical Sciences, Creighton University School of Medicine, Omaha, NE, USA.
Nicholas Y PalermoHolland Computing Center, University of Nebraska-Lincoln, Lincoln, NE, USA.
Justin G MadsonMidwest Dermatology Clinic, Omaha, NE, USA.
Sándor LovasDepartment of Biomedical Sciences, Creighton University School of Medicine, Omaha, NE, USA.
Laura A HansenDepartment of Biomedical Sciences, Creighton University School of Medicine, Omaha, NE, USA.
Creighton University · USCentral Dermatology · USUniversity of Nebraska–Lincoln · US

Funding

Targeting aberrant anti-apoptotic signaling for prevention of skin cancerR01CA253573 · NCI · CREIGHTON UNIVERSITY · PI HANSEN, LAURA A · 2020 to 2024
$1.6M
NCI NIH HHS R01 CA253573
6 · The paper itself

Abstract

More than a million cases of cutaneous squamous cell carcinoma are diagnosed in the USA each year, and its incidence is increasing. Most of these malignancies arise from premalignant lesions, providing an opportunity for intervention before malignant progression. We previously documented how cytoplasmic mislocalization of CDC25A in premalignant and malignant skin cancers confers resistance to apoptotic cell death via a mechanism that depends on its interaction with 14-3-3ε. From these data, we hypothesized that 14-3-3ε overexpression drives skin tumor development and progression, such that targeting 14-3-3ε may be a useful strategy for skin cancer treatment. Like CDC25A, 14-3-3ε was overexpressed and mislocalized to the cytoplasm of both benign and malignant human skin cancer. Skin-targeted deletion of the 14-3-3ε gene reduced skin tumor development by 75% and blocked malignant progression. 14-3-3ε suppressed apoptosis through activation of Akt, leading to inhibition of BCL2 associated agonist of cell death and upregulation of Survivin. Using virtual tetrapeptide libraries, we developed a novel peptide that specifically blocked 14-3-3ε heterodimerization and thereby prevented its interaction with CDC25A. The peptide reduced prosurvival signaling, killed skin cancer cells and reduced skin tumor growth in xenograft. Normal skin keratinocytes were unaffected by inhibition or deletion of 14-3-3ε. Thus, targeting of 14-3-3ε dimerization is a promising strategy for the treatment of premalignant skin lesions.

Indexed as

14-3-3 Proteins9,10-Dimethyl-1,2-benzanthraceneAnimalsAntineoplastic AgentsApoptosisCarcinogensCarcinoma, Squamous Cellcdc25 PhosphatasesCell Line, TumorCytoplasmFemaleHumansKeratinocytesMaleMiceMice, Knockout12-O-tetradecanoylphorbol-1,3-acetate14-3-3 Proteins9,10-Dimethyl-1,2-benzanthraceneAntineoplastic AgentsCarcinogensCDC25A protein, humancdc25 PhosphatasesTetradecanoylphorbol AcetateYWHAE protein, humanYwhae protein, mouse

Identifiers

PMID32816038
PMCPMC7905839
OpenAlexW3080271184

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.