NADPH oxidase 4 regulates anoikis resistance of gastric cancer cells through the generation of reactive oxygen species and the induction of EGFR

被引：0
作者：
Shangce Du
Ji Miao
Zhouting Zhu
En Xu
Linsen Shi
Shichao Ai
Feng Wang
Xing Kang
Hong Chen
Xiaofeng Lu
Wenxian Guan
Xuefeng Xia
机构：
[1] Drum Tower Clinical Medical College of Nanjing Medical University,Department of General Surgery
[2] The Affiliated Hospital of Nanjing University Medical School,Department of General Surgery, Nanjing Drum Tower Hospital
来源：
Cell Death & Disease | / 9卷
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摘要：
Anoikis is a type of programmed cell death induced by detachment from the extracellular matrix. In cancer cells, anoikis resistance is essential for cancer cell survival in blood circulation and distant metastasis. However, the mechanisms behind anoikis resistance of gastric cancer remain largely unknown. Herein, we demonstrate that NADPH oxidase 4 (NOX4) expression and reactive oxygen species (ROS) generation are upregulated in suspension gastric cell cultures compared with adherent cultures. Silencing of NOX4 decreases ROS generation and downregulates EGFR, sensitizing cells to anoikis. NOX4 overexpression upregulates ROS and EGFR levels and promotes anoikis resistance. NOX4 depletion inhibits gastric cancer survival in blood circulation and attenuates distant metastasis. NOX4 expression is correlated with EGFR expression in patients. In conclusion, induction of NOX4 expression by detachment promotes anoikis resistance of gastric cancer through ROS generation and downstream upregulation of EGFR, which is critical for the metastatic progression of gastric cancer.
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  • [11] Griendling KK(2009)Expression of NADPH oxidase homologues and accessory genes in human cancer cell lines, tumours and adjacent normal tissues Free Radic. Res. 43 523-532
  • [12] Liou GY(2014)NADPH oxidase NOX4 supports renal tumorigenesis by promoting the expression and nuclear accumulation of HIF2alpha Cancer Res. 74 3501-3511
  • [13] Storz P(2014)Wild-type and mutant p53 differentially regulate NADPH oxidase 4 in TGF-b-mediated migration of human lung and breast epithelial cells Br. J. Cancer 110 2569-2582
  • [14] Schumacker PT(2017)The NADPH oxidase NOX4 represses epithelial to amoeboid transition and efficient tumour dissemination Oncogene 36 3002-3014
  • [15] Roy K(2009)Tks5-dependent, nox-mediated generation of reactive oxygen species is necessary for invadopodia formation Sci. Signal. 2 ra53-1531
  • [16] Bedard K(1982)A native 170,000 epidermal growth factor receptor-kinase complex from shed plasma membrane vesicles J. Biol. Chem. 257 1523-6000
  • [17] Krause KH(2012)Impact of expression of human epidermal growth factor receptors EGFR and ERBB2 on survival in stage II/III gastric cancer Clin. Cancer Res. 18 5992-3029
  • [18] Juhasz A(2008)Impact of insulin-like growth factor type 1 receptor, epidermal growth factor receptor, and HER2 expressions on outcomes of patients with gastric cancer Clin. Cancer Res. 14 3022-740
  • [19] Gregg JL(2003)Integrins and EGFR coordinately regulate the pro-apoptotic protein Bim to prevent anoikis Nat. Cell Biol. 5 733-455
  • [20] Boudreau HE(2013)CCN2 inhibits lung cancer metastasis through promoting DAPK-dependent anoikis and inducing EGFR degradation Cell Death Differ. 20 443-99
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