1. Reciprocal activation between IL-6/STAT3 and NOX4/Akt signalings promotes proliferation and survival of non-small cell lung cancer cells
- Author
-
Jincai Hou, Zhicheng Yang, Juan Li, Bing Liu, Cheng Zeng, Cuixiang Zhang, Jian-Xun Liu, Min Zhang, and Tian Lan
- Subjects
STAT3 Transcription Factor ,Lung Neoplasms ,Cell Survival ,Blotting, Western ,Mice, Nude ,Antineoplastic Agents ,Proinflammatory cytokine ,Cell Line ,NOX4 ,Carcinoma, Non-Small-Cell Lung ,Cell Line, Tumor ,oxidative stress ,Animals ,Humans ,STAT3 ,Protein kinase B ,neoplasms ,non-small cell lung cancer ,Cell Proliferation ,IL-6 ,NADPH oxidase ,biology ,Cell growth ,urogenital system ,Interleukin-6 ,Antibodies, Monoclonal ,NADPH Oxidases ,Immunohistochemistry ,Cell biology ,respiratory tract diseases ,Oncology ,Cell culture ,NADPH Oxidase 4 ,Cancer research ,biology.protein ,cardiovascular system ,Female ,RNA Interference ,Signal transduction ,Reactive Oxygen Species ,Proto-Oncogene Proteins c-akt ,Research Paper ,Signal Transduction - Abstract
Inflammatory cytokines and oxidative stress are two critical mediators in inflammation-associated cancer. Interleukin-6 (IL-6) is one of the most critical tumor-promoting cytokines in non-small cell lung cancer (NSCLC). In our recent study, we confirmed that NADPH oxidase 4 (NOX4), an important source of reactive oxygen species (ROS) production in NSCLC cells, promotes malignant progression of NSCLC. However, whether the crosstalk of NOX4 and IL-6 signalings exists in NSCLC remains undentified. In this study, we show that NOX4 expression is positively correlated with IL-6 expression in NSCLC tissues. Exogenous IL-6 treatment significantly enhances NOX4/ROS/Akt signaling in NSCLC cells. NOX4 also enhances IL-6 production and activates IL-6/STAT3 signaling in NSCLC cells. Specifically, NOX4 is confirmed to functionally interplay with IL-6 to promote NSCLC cell proliferation and survival. The in vivo results were similar to those obtained in vitro. These data indicate a novel NOX4-dependent link among IL-6 in the NSCLC microenvironment, oxidative stress in NSCLC cells and autocrined IL-6 in NSCLC cells. NOX4/Akt and IL-6/STAT3 signalings can reciprocally and positively regulate each other, leading to enhanced NSCLC cell proliferation and survival. Therefore, NOX4 may serve as a promising target against NSCLC alone with IL-6 signaling.
- Published
- 2015