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HDAC inhibitors suppress the proliferation, migration and invasiveness of human head and neck squamous cell carcinoma cells via p63‑mediated tight junction molecules and p21‑mediated growth arrest

  • Authors:
    • Akito Kakiuchi
    • Takuya Kakuki
    • Kizuku Ohwada
    • Makoto Kurose
    • Atsushi Kondoh
    • Kazufumi Obata
    • Kazuaki Nomura
    • Ryo Miyata
    • Yakuto Kaneko
    • Takumi Konno
    • Takayuki Kohno
    • Tetsuo Himi
    • Ken-Ichi Takano
    • Takashi Kojima
  • View Affiliations / Copyright

    Affiliations: Department of Otolaryngology, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo 060‑8556, Japan, Department of Cell Science, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo 060‑8556, Japan
    Copyright: © Kakiuchi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 46
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    Published online on: March 1, 2021
       https://doi.org/10.3892/or.2021.7997
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Abstract

In human head and neck squamous cell carcinoma (HNSCC), the invasion and metastatic properties of cancer cells are promoted by junctional adhesion molecule‑A (JAM‑A) and claudin‑1; these are epithelial tight junction molecules regulated by histone deacetylases (HDACs) and transcription factor p63. HDAC expression is reportedly upregulated in HNSCC, and HDAC inhibitors suppress cancer cell proliferation by initiating proliferative arrest or apoptosis. However, little is known of the anti‑cancer mechanisms of HDAC inhibitors in HNSCC. Thus, in the present study, the HNSCC Detroit 562 cell line and primary cultured HNSCC cells were treated with HDAC inhibitors to investigate their effects in HNSCC. Higher expression of p63, HDAC1, JAM‑A and claudin‑1 was observed in HNSCC tissues compared with the adjacent dysplastic regions. In Detroit 562 cells, treatment with trichostatin A (TSA), an inhibitor of HDAC1 and 6, downregulated the expression of p63, JAM‑A and claudin‑1, and upregulated that of acetylated tubulin; conversely, p63 knockdown resulted in the downregulation of JAM‑A and claudin‑1. Collectively, inhibiting HDAC suppressed the migration and invasiveness of cancer cells. In addition, treatment with TSA suppressed cancer cell proliferation via G2/M arrest, as well as upregulating p21 and downregulating cyclin D1 expression. TSA also downregulated the expression of epidermal growth factor receptor (EGFR) and phospho‑ERK1/2. p63 knockdown and treatment with an EGFR inhibitor induced G1 arrest and downregulated EGFR and phospho‑ERK1/2 levels, respectively. HDAC inhibition also suppressed the migration and invasiveness of primary cultured HNSCC cells. Collectively, the results of the present study indicate that HDAC inhibitors suppress the proliferation, migration and invasiveness of HNSCC by downregulating the p63‑mediated tight junction molecules JAM‑A and claudin‑1, and inducing p63 or p21‑mediated growth arrest.
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Copy and paste a formatted citation
Spandidos Publications style
Kakiuchi A, Kakuki T, Ohwada K, Kurose M, Kondoh A, Obata K, Nomura K, Miyata R, Kaneko Y, Konno T, Konno T, et al: HDAC inhibitors suppress the proliferation, migration and invasiveness of human head and neck squamous cell carcinoma cells via p63‑mediated tight junction molecules and p21‑mediated growth arrest. Oncol Rep 45: 46, 2021.
APA
Kakiuchi, A., Kakuki, T., Ohwada, K., Kurose, M., Kondoh, A., Obata, K. ... Kojima, T. (2021). HDAC inhibitors suppress the proliferation, migration and invasiveness of human head and neck squamous cell carcinoma cells via p63‑mediated tight junction molecules and p21‑mediated growth arrest. Oncology Reports, 45, 46. https://doi.org/10.3892/or.2021.7997
MLA
Kakiuchi, A., Kakuki, T., Ohwada, K., Kurose, M., Kondoh, A., Obata, K., Nomura, K., Miyata, R., Kaneko, Y., Konno, T., Kohno, T., Himi, T., Takano, K., Kojima, T."HDAC inhibitors suppress the proliferation, migration and invasiveness of human head and neck squamous cell carcinoma cells via p63‑mediated tight junction molecules and p21‑mediated growth arrest". Oncology Reports 45.4 (2021): 46.
Chicago
Kakiuchi, A., Kakuki, T., Ohwada, K., Kurose, M., Kondoh, A., Obata, K., Nomura, K., Miyata, R., Kaneko, Y., Konno, T., Kohno, T., Himi, T., Takano, K., Kojima, T."HDAC inhibitors suppress the proliferation, migration and invasiveness of human head and neck squamous cell carcinoma cells via p63‑mediated tight junction molecules and p21‑mediated growth arrest". Oncology Reports 45, no. 4 (2021): 46. https://doi.org/10.3892/or.2021.7997
Copy and paste a formatted citation
x
Spandidos Publications style
Kakiuchi A, Kakuki T, Ohwada K, Kurose M, Kondoh A, Obata K, Nomura K, Miyata R, Kaneko Y, Konno T, Konno T, et al: HDAC inhibitors suppress the proliferation, migration and invasiveness of human head and neck squamous cell carcinoma cells via p63‑mediated tight junction molecules and p21‑mediated growth arrest. Oncol Rep 45: 46, 2021.
APA
Kakiuchi, A., Kakuki, T., Ohwada, K., Kurose, M., Kondoh, A., Obata, K. ... Kojima, T. (2021). HDAC inhibitors suppress the proliferation, migration and invasiveness of human head and neck squamous cell carcinoma cells via p63‑mediated tight junction molecules and p21‑mediated growth arrest. Oncology Reports, 45, 46. https://doi.org/10.3892/or.2021.7997
MLA
Kakiuchi, A., Kakuki, T., Ohwada, K., Kurose, M., Kondoh, A., Obata, K., Nomura, K., Miyata, R., Kaneko, Y., Konno, T., Kohno, T., Himi, T., Takano, K., Kojima, T."HDAC inhibitors suppress the proliferation, migration and invasiveness of human head and neck squamous cell carcinoma cells via p63‑mediated tight junction molecules and p21‑mediated growth arrest". Oncology Reports 45.4 (2021): 46.
Chicago
Kakiuchi, A., Kakuki, T., Ohwada, K., Kurose, M., Kondoh, A., Obata, K., Nomura, K., Miyata, R., Kaneko, Y., Konno, T., Kohno, T., Himi, T., Takano, K., Kojima, T."HDAC inhibitors suppress the proliferation, migration and invasiveness of human head and neck squamous cell carcinoma cells via p63‑mediated tight junction molecules and p21‑mediated growth arrest". Oncology Reports 45, no. 4 (2021): 46. https://doi.org/10.3892/or.2021.7997
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