Reactive oxygen species (ROS) are signaling molecules that determine cellular fate. In tumor progression, ROS have been suggested to function as a dual cell controller. They could induce cellular proliferation in low levels while inhibiting cellular proliferation in high levels. ROS can be produced by NOXX, a member of NADPH oxidase family. Here, we present that an increase in NOXX levels by activation of STAT5 are critical in tumor progression by comparing the NOXX levels of breast and lung tumor tissues to those of normal tissues. Consistently, depletion of NOXX causes tumor suppression of lung and breast cancer cells, and expression of NOXX induces proliferation of normal lung cells. Notably, we found that cisplatin, an antineoplastic agent, increases NOXX activity and inhibits cellular proliferation. Specifically, cisplatin activates NOXX to induce a high level of ROS in multiple ways through (i) an increase in NOXX levels, (ii) an increase in levels of c-abl which is an activator of NOXX, and (iii) a release of Ca2+, the other activator of NOXX. Together, NOXX is a double-edged sword for tumorigenesis in lung and breast cancers by modulating ROS levels, and will be a promising target for cancer therapy.
Citation Format: So Hee Dho, Ji Young Kim, Chang-Jin Kim, William M. Nauseef, So-Young Choi, Kwang-Pyo Lee, Ki-Sun Kwon. NOXX: Friend or foe for cellular proliferation. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2916. doi:10.1158/1538-7445.AM2013-2916