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Purpose <p>Salivary 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.</p> Methods <p>The 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.</p> Results <p>Treatment 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.</p> Conclusions <p>p63 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.</p>

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

  • 期刊论文

  • 发表日期：

    2026年1月6日

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  • Masahiko Oyanagi,
  • Takumi Konno,
  • Soshi Nishida,
  • Takayuki Kohno,
  • Ikuto Kimura,
  • Masaya Nakano,
  • Kizuku Ohwada,
  • Takuya Kakuki,
  • Kazufumi Obata,
  • Akito Kakiuchi,
  • Makoto Kurose,
  • Kenichi Takano,
  • Takashi Kojima

摘要

Purpose

Salivary 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.

Methods

The 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.

Results

Treatment 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.

Conclusions

p63 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.