Reversion-inducing cysteine-rich protein with Kazal motifs interferes with epidermal growth factor receptor signaling

• Kitajima Shunsuke

• Miki T.

• Takegami Yujiro

• Kido Y.

• Noda M.

• Hara Eiji

• Shamma Awad

• Takahashi Chiaki

• 北嶋 俊輔

• 高橋 智聡

書誌事項

タイトル別名

• Reversion‐inducing cysteine‐rich protein with Kazal motifs interferes with epidermal growth factor receptor signaling

抄録

金沢大学がん研究所

The reversion-inducing cysteine-rich protein with Kazal motifs (RECK) gene had been isolated as an antagonist to RAS signaling; however, the mechanism of its action is not clear. In this study, the effect of loss of RECK function was assessed in various ways and cell systems. Successive cell cultivation of mouse embryonic fibroblasts (MEFs) according to 3T3 protocol revealed that the germline knockout of RECK confers accelerated cell proliferation and early escape from cellular senescence associated with downregulation of p19 Arf, Trp53 and p21Cdkn1a. In contrast, short hairpin RNA-mediated depletion of RECK induced irreversible growth arrest along with several features of the Arf, Trp53 and Cdkn1a-dependent cellular senescence. Within 2 days of RECK depletion, we observed a transient increase in protein kinase B (AKT) and extracellular signal-regulated kinase (ERK) phosphorylation associated with an upregulated expression of cyclin D1, p19Arf, Trp53, p21Cdkn1a and Sprouty 2. On further cultivation, RAS, AKT and ERK activities were then downregulated to a level lower than control, indicating that RECK depletion leads to a negative feedback to RAS signaling and subsequent cellular senescence. In addition, we observed that epidermal growth factor receptor (EGFR) activity was transiently upregulated by RECK depletion in MEFs, and continuously downregulated by RECK overexpression in colon cancer cells. These findings indicate that RECK is a novel modulator of EGFR signaling. © 2011 Macmillan Publishers Limited All rights reserved.

収録刊行物

• Oncogene

  Oncogene 30 (6), 737-750, 2011-02-10

  Nature Publishing Group

キーワード

• EGFR
• MMP
• negative feedback
• RAS
• RECK
• senescence

詳細情報

• CRID: 1390294496044146688
• NII論文ID: 120002907445
• NII書誌ID: AA10687380
• ISSN: 09509232
• ISSN: 14765594
• DOI: 10.24517/00027532
• DOI: 10.1038/onc.2010.448
• Web Site: http://hdl.handle.net/2297/27079
• Web Site: https://www.nature.com/articles/onc2010448.pdf
• Web Site: https://www.nature.com/articles/onc2010448
• 本文言語コード: en
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