Evidence map›Paper›PMID 41495522›Full record

ArticleEuropean archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery2026

Reciprocity between p63 and p21 via TNFα/NF-κB signaling in p63-positive salivary duct adenocarcinoma cell.

Masahiko Oyanagi, Takumi Konno, Soshi Nishida, Takayuki Kohno, Ikuto Kimura, Masaya Nakano, Kizuku Ohwada, Takuya Kakuki, Kazufumi Obata, Akito Kakiuchi and 3 more

Abstract read
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In one paragraph

Article in European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Review
  2. Comment on "Reciprocity between p63 and p21 via TNFα/NF-κB signaling in p63-positive salivary duct adenocarcinoma cell".European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2026
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

Masahiko Oyanagi *Department of Otolaryngology - Head and Neck surgery, Sapporo Medical University School of Medicine, Minami 1-jo, Nishi 17-chome, Chuo-ku, Sapporo, 060-8556, Japan.
Takumi Konno *Department of Cell Science, Institute of Cancer Research, Sapporo Medical University School of Medicine, Minami 1-jo, Nishi 17-chome, Chuo-ku, Sapporo, 060-8556, Japan. tkonno@sapmed.ac.jp.ORCID http://orcid.org/0000-0002-9339-3864
Soshi Nishida *Department of Otolaryngology - Head and Neck surgery, Sapporo Medical University School of Medicine, Minami 1-jo, Nishi 17-chome, Chuo-ku, Sapporo, 060-8556, Japan.
Takayuki KohnoDepartment of Cell Science, Institute of Cancer Research, Sapporo Medical University School of Medicine, Minami 1-jo, Nishi 17-chome, Chuo-ku, Sapporo, 060-8556, Japan.
Ikuto KimuraDepartment of Cell Science, Institute of Cancer Research, Sapporo Medical University School of Medicine, Minami 1-jo, Nishi 17-chome, Chuo-ku, Sapporo, 060-8556, Japan.
Masaya NakanoDepartment of Otolaryngology - Head and Neck surgery, Sapporo Medical University School of Medicine, Minami 1-jo, Nishi 17-chome, Chuo-ku, Sapporo, 060-8556, Japan.
Kizuku OhwadaDepartment of Otolaryngology - Head and Neck surgery, Sapporo Medical University School of Medicine, Minami 1-jo, Nishi 17-chome, Chuo-ku, Sapporo, 060-8556, Japan.
Takuya KakukiDepartment of Otolaryngology - Head and Neck surgery, Sapporo Medical University School of Medicine, Minami 1-jo, Nishi 17-chome, Chuo-ku, Sapporo, 060-8556, Japan.
Kazufumi ObataDepartment of Otolaryngology - Head and Neck surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, 259-1193, Japan.
Akito KakiuchiDepartment of Otolaryngology - Head and Neck surgery, Sapporo Medical University School of Medicine, Minami 1-jo, Nishi 17-chome, Chuo-ku, Sapporo, 060-8556, Japan.
Makoto KuroseDepartment of Otolaryngology - Head and Neck surgery, Sapporo Medical University School of Medicine, Minami 1-jo, Nishi 17-chome, Chuo-ku, Sapporo, 060-8556, Japan.
Kenichi TakanoDepartment of Otolaryngology - Head and Neck surgery, Sapporo Medical University School of Medicine, Minami 1-jo, Nishi 17-chome, Chuo-ku, Sapporo, 060-8556, Japan.
Takashi KojimaDepartment of Cell Science, Institute of Cancer Research, Sapporo Medical University School of Medicine, Minami 1-jo, Nishi 17-chome, Chuo-ku, Sapporo, 060-8556, Japan.

Funding

Japan Society for the Promotion of Science 21K09610Japan Society for the Promotion of Science 22K09687Japan Society for the Promotion of Science 22K09729Japan Society for the Promotion of Science 23K15866
6 · The paper itself

Abstract

purposeSalivary gland cancer is a rare malignant tumor, and the expression of p63 is increased in salivary gland tumors. p63 is a well-known gene playing an important role in controlling cell differentiation, cell cycle arrest, cell migration, and apoptosis that is regulated by various signaling pathways. Similarly, the p21 gene, induced either dependent on or independently of p53, plays an important role in controlling cell cycle progression and suppressing tumor growth. Therefore, in salivary gland cancer, p63 and p21 may interact directly or indirectly to influence cell cycle regulation, apoptosis, and other cellular processes and p63 might be a potential therapeutic target of salivary gland cancer. In this study, we aimed to investigate the reciprocity between p63 and p21 via TNFα/NF-κB signaling in p63-positive salivary duct adenocarcinoma.

methodsThe p63-positive salivary duct adenocarcinoma cell line A253 was treated with TNFα, curcumin (a phytochemical widely used to inhibit NF-κB activation), and other growth factors and signaling inhibitors. Western blot assay, immunocytochemistry, cell cycle assay, and migration assay were utilized in this assay.

resultsTreatment with TNFα decreased p63 expression and increased p21 expression. Treatment with curcumin enhanced the effects of TNFα-related signaling on p63 downregulation and p21 upregulation, while pretreatment with an anti-TNFα antibody, TGF-β type I receptor inhibitor EW-7196 and JNK inhibitor SP600125 inhibited the effects. Treatment with HDAC inhibitors decreased p63 expression, increased p21 expression and inhibited cell migration and cell proliferation.

conclusionsp63 expression and its functions are regulated via various signaling pathways, and there is reciprocity between p63 and p21 via TNFα/NF-κB-related signaling in p63-positive salivary duct adenocarcinoma cells. Because apoptosis was not directly assessed in this study, our conclusions are limited to p63/p21 expression, cell cycle distribution and cell migration.

Indexed as

Cell migrationCurcuminP21P63Salivary gland duct adenocarcinomaTNFα

Identifiers

PMID41495522

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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.