Abstract 1247: NOX4 P62 regulates tuberculous fibrosis promoted tumorigenic potential

Abstract

Abstract Background Increased incidence of lung cancer in subjects with previous tuberculous infection was reported in epidemiologic data. NOX4 signaling contributes to tuberculous pleural fibrosis and lung cancer proliferation, respectively. The objective of this study was to investigate the role of NOX4 in tuberculous pleurisy-assisted tumorigenicity both in vitro and in vivo. Methods After pleural mesothelial cells from WT and NOX4 KO C57BL/6 mice were stimulated with Heat-Killed mycobacterium tuberculosis (HKMT) for 24 hour, cellular interactions between mesothelial cell and cancer cell were evaluated by using transwell invasion assay and wound healing assay. A murine model injected with cancer at 4 weeks after Mycobacterium bovis bacillus Calmette-Guérin (BCG) pleural infection were used to validate the contribution of tuberculous fibrosis to tumor invasion. Results HKMT -stimulated mesothelial cells induced enhanced invasion and migration potential of lung cancer cells in a NOX4-dependent manner. The inhibition of NOX4 signaling exerted a negative effect on the metastatic potential of lung cancer by tuberculous fibrosis in mice model. The expression of inflammatory cytokines like TNF-a, TGF-β and IL-6 was enhanced in the WT-BCG+CA than WT+PBS+CA and NOX4 KO+BCG+CA. The expression of P62 in lung tissue was higher in the WT-BCG+CA than WT+PBS+CA and NOX4 KO+BCG+CA. Discussions Our results suggest that NOX4 and autophagy signaling changed by tuberculous fibrosis could result enhanced tumorigenic potential. NOX4-P62 might seve as a target for the development of anti-tuberculous fibrosis and anti-cancer drugs. Citation Format: Yoonki Hong, Seong-Ji Woo, Youngmi Kim, Ji Young Hong. NOX4 P62 regulates tuberculous fibrosis promoted tumorigenic potential [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1247.