CARF (Collaborator of ARF) overexpression in p53‐deficient cells promotes carcinogenesis

DOI Web Site Web Site Web Site Web Site ほか1件をすべて表示 一部だけ表示 被引用文献1件 参考文献34件 オープンアクセス

書誌事項

公開日
2015-08-04
資源種別
journal article
権利情報
  • http://onlinelibrary.wiley.com/termsAndConditions#vor
DOI
  • 10.1016/j.molonc.2015.07.003
公開者
Wiley

この論文をさがす

説明

<jats:p>Collaborator of ARF (CARF), initially identified as a binding partner of ARF (Alternate Reading Frame), has been shown to activate ARF–p53 pathway by multiple ways including stabilization of ARF and p53 tumor suppressor proteins, and transcriptional repression of a p53 antagonist, HDM2. Level of CARF expression was shown to determine fate of cells. Whereas its knockdown caused apoptosis, its over‐ and super‐expressions caused senescence and increase in malignant properties of cancer cells, respectively, and were closely linked to increase and decrease in p53 activity. Using p53‐compromised cancer cells, we demonstrate that CARF induces growth arrest when wild type p53 is present and in p53‐absence, it promotes carcinogenesis. Biochemical analyses on CARF‐induced molecular signaling revealed that in p53‐null cells, it caused transcriptional repression of p21WAF1 leading to increase in CDK4, CDK6, pRb and E2F1 resulting in continued cell cycle progression. Furthermore, it instigated increase in migration and invasion of cancer cells that was marked by upregulation of MMP2, MMP3, MMP9, uPA, several interleukins and VEGF expression. Consistent with these findings, we found that human clinical samples of epithelial and glial cancers (frequently marked by loss of p53 function) possessed high level of CARF expression showing a relationship with cancer aggressiveness. The data demonstrated that CARF could be considered as a diagnostic marker and a therapeutic target in p53‐compromised malignancies.</jats:p>

収録刊行物

被引用文献 (1)*注記

もっと見る

参考文献 (34)*注記

もっと見る

関連プロジェクト

もっと見る

キーワード

問題の指摘

ページトップへ