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Prolonged cetuximab treatment promotes p27Kip1-mediated G1 arrest and autophagy in head and neck squamous cell carcinoma
https://repo.qst.go.jp/records/84322
https://repo.qst.go.jp/records/8432294e1ae32-ca06-4642-8e0c-ba28828cd011
Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2021-09-30 | |||||
タイトル | ||||||
タイトル | Prolonged cetuximab treatment promotes p27Kip1-mediated G1 arrest and autophagy in head and neck squamous cell carcinoma | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
アクセス権 | ||||||
アクセス権 | metadata only access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
著者 |
Okuyama, Kohei
× Okuyama, Kohei× Keiji, Suzuki× Naruse, Tomofumi× Tsuchihashi, Hiroki× Yanamoto, Souichi× Kaida, Atsushi× Miura, Masahiko× Umeda, Masahiro× Shunichi, Yamashita× Keiji, Suzuki× Shunichi, Yamashita |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Cetuximab, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody, is an efficient anti-tumor therapeutic agent that inhibits the activation of EGFR; however, data related to the cellular effects of prolonged cetuximab treatment are limited. In this study, the long-term cellular outcome of prolonged cetuximab treatment and the related molecular mechanism were explored in a head and neck squamous cell carcinoma cell line constitutively expressing a fluorescent ubiquitination-based cell cycle indicator. Fluorescent time-lapse imaging was used to assess clonal growth, cell motility, and cell-cycle progression. Western blot analysis was performed to measure the level of phosphorylation and protein-expression following cetuximab treatment. Over 5 days cetuximab treatment decreased cell motility and enhanced G1 phase cell arrest in the central region of the colonies. Significantly decreased phosphorylation of retinoblastoma, Skp2, and Akt-mTOR proteins, accumulation of p27Kip1, and induction of type II LC3B were observed over 8 days cetuximab treatment. Results of the present study elucidate the cetuximab-dependent inhibition of cell migration, resulting in high cell density-related stress and persistent cell-cycle arrest at G1 phase culminating in autophagy. These findings provide novel molecular insights related to the anti-tumor effects of prolonged cetuximab treatment with the potential to improve future therapeutic strategy. | |||||
書誌情報 |
Scientific Reports 巻 11, p. 5259, 発行日 2021-03 |
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出版者 | ||||||
出版者 | Nature | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 2045-2322 | |||||
DOI | ||||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1038/s41598-021-84877-4 | |||||
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識別子タイプ | URI | |||||
関連識別子 | https://www.nature.com/articles/s41598-021-84877-4 |