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日本語AIでPubMedを検索

PubMedの提供する医学論文データベースを日本語で検索できます。AI(Deep Learning)を活用した機械翻訳エンジンにより、精度高く日本語へ翻訳された論文をご参照いただけます。
Theranostics.2020;10(16):7083-7099. thnov10p7083. doi: 10.7150/thno.44744.Epub 2020-05-30.

Oleic acid-induced NOX4 is dependent on ANGPTL4 expression to promote human colorectal cancer metastasis.

  • Chih-Jie Shen
  • Kwang-Yu Chang
  • Bo-Wen Lin
  • Wei-Ting Lin
  • Che-Min Su
  • Jhih-Peng Tsai
  • Yu-Han Liao
  • Liang-Yi Hung
  • Wen-Chang Chang
  • Ben-Kuen Chen
PMID: 32641980 PMCID: PMC7330862. DOI: 10.7150/thno.44744.

抄録

Colorectal cancer (CRC) progression and related mortality are highly associated with metabolic disorders. However, the molecular mechanism involved in the regulation of hyperlipidemia-associated CRC metastasis remains unclear. This study aimed to investigate the effects of angiopoietin-like 4 (ANGPTL4) on NADPH oxidase 4 (NOX4) expression and reactive oxygen species (ROS) production, which might provide new targets for improving outcomes in patients with hyperlipidemia-associated CRC metastasis. The clinical relevance of relationship between NOX4 expression and ANGPTL4 was examined in CRC patients by the Oncomine and TCGA data set. Expressions of NOX4, epithelial-mesenchymal transition (EMT) markers, and gene regulation of NOX4 in free fatty acids (FFAs)-treated CRC cells were determined. The FFAs-triggered metastatic ability of CRC cells under treatments of antioxidants or knockdown of NOX4, ANGPTL4, and MMPs was evaluated and . In addition, effects of antioxidants and depletion of metastasis-associated molecules on the correlation between ROS production and FFAs-promoted CRC metastasis were also clarified. In this study, we found that the induction of NOX4, followed by the increased ROS was essential for oleic acid (OA)-promoted CRC cell metastasis. The depletion of ANGPTL4 significantly inhibited c-Jun-mediated transactivation of NOX4 expression, accompanied with reduced levels of ROS, MMP-1, and MMP-9, resulting in the disruption of OA-promoted CRC cell metastasis. Moreover, knockdown of ANGPTL4, NOX4, MMP-1, and MMP-9 or the treatment of antioxidants dramatically inhibited circulating OA-enhanced tumor cell extravasation and metastatic seeding of tumor cells in lungs, indicating that the ANGPTL4/NOX4 axis was critical for dyslipidemia-associated tumor metastasis. The coincident expression of NOX4 and ANGPTL4 in CRC tumor specimens provides the insight into the potential therapeutic targets for the treatment of dyslipidemia-associated CRC metastasis.

© The author(s).