AUTHOR=Zulato Elisabetta , Ciccarese Francesco , Nardo Giorgia , Pinazza Marica , Agnusdei Valentina , Silic-Benussi Micol , Ciminale Vincenzo , Indraccolo Stefano 

TITLE=Involvement of NADPH Oxidase 1 in Liver Kinase B1-Mediated Effects on Tumor Angiogenesis and Growth

JOURNAL=Frontiers in Oncology

VOLUME=8

YEAR=2018

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2018.00195

DOI=10.3389/fonc.2018.00195

ISSN=2234-943X

ABSTRACT=<p>The liver kinase B1 (<italic>LKB1</italic>) gene is a tumor suppressor with an established role in the control of cell metabolism and oxidative stress. However, whether dis-regulated oxidative stress promotes growth of LKB1-deficient tumors remains substantially unknown. Through <italic>in vitro</italic> studies, we observed that loss of LKB1 perturbed expression of several genes involved in reactive oxygen species (ROS) homeostasis. In particular, this analysis evidenced strongly up-modulated NADPH oxidase 1 (<italic>NOX1</italic>) transcript levels in tumor cells lacking LKB1. NOX1 accounted in part for enhanced cytotoxic effects of H<sub>2</sub>O<sub>2</sub>-induced oxidative stress in A549 LKB1-deficient tumor cells. Notably, genetic and pharmacologic inhibition of NOX1 activity reduced angiogenesis and growth of A549 tumors in mice. These results suggest that NOX1 inhibitors could counteract ROS production and the angiogenic switch in LKB1-deficient tumors.</p>