Details

Autor(en) / Beteiligte

• Du, Shangce
• Miao, Ji
• Zhu, Zhouting
• Xu, En
• Shi, Linsen
• Ai, Shichao
• Wang, Feng
• Kang, Xing
• Chen, Hong
• Lu, Xiaofeng
• Guan, Wenxian
• Xia, Xuefeng

Titel

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

Ist Teil von

• Cell death & disease, 2018-09, Vol.9 (10), p.948-18, Article 948

Ort / Verlag

England: Springer Nature B.V

Erscheinungsjahr

2018

Quelle

EZB-FREE-00999 freely available EZB journals

Beschreibungen/Notizen

• 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.