ArticleCarcinogenesis2021
Targeting 14-3-3ε activates apoptotic signaling to prevent cutaneous squamous cell carcinoma.
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.
What it found
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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.
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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.
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Who cites it
12 citing papers in PubMed, 19 citations in OpenAlex.
- p53 overexpression counteracts the pro-survival effect of Bcl-2 by restoring MAMs function in cutaneous squamous cell carcinoma.Cell division · 2026Article
- The human Flower isoform hFWE4 facilitates cornification in cutaneous squamous cell carcinoma.JID innovations : skin science from molecules to population health · 2026Article
- The Importance of 14-3-3 Proteins in Colorectal Cancer Regulation: Mechanisms of Function and Clinical Opportunities.BioMed research international · 2026Review
- Ligand recognition by 14-3-3 proteins requires negative charges but not necessarily phosphorylation.FEBS letters · 2025Article
- Negative Charges, Not Necessary Phosphorylation, are Required for Ligand Recognition by 14-3-3 Proteins.bioRxiv : the preprint server for biology · 2024Article
- circSORBS1 inhibits lung cancer progression by sponging miR-6779-5p and directly binding RUFY3 mRNA.Journal of translational medicine · 2024Article
- Arnicolide C Suppresses Tumor Progression by Targeting 14-3-3θ in Breast Cancer.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Optimizing Phosphopeptide Structures That Target 14-3-3ε in Cutaneous Squamous Cell Carcinoma.ACS omega · 2024Article
- Optimizing Phosphopeptide Structures That Target 14-3-3ε in Cutaneous Squamous Cell Carcinoma.bioRxiv : the preprint server for biology · 2023Article
- The Phosphofurin Acidic Cluster Sorting Protein 2 (PACS-2) E209K Mutation Responsible for PACS-2 Syndrome Increases Susceptibility to Apoptosis.ACS omega · 2022Article
- Basic approaches, challenges and opportunities for the discovery of small molecule anti-tumor drugs.American journal of cancer research · 2021Review
- Targeting 14-3-3ε-CDC25A interactions to trigger apoptotic cell death in skin cancer.Oncotarget · 2020Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
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.
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Registered trials
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.