AQP3-mediated H₂ O₂ uptake inhibits LUAD autophagy by inactivating PTEN.

ABSTRACT: It is widely accepted that redox reprogramming participates in malignant transformation of lung adenocarcinoma (LUAD). However, the source of excessive reactive oxygen species (ROS) and the downstream signaling regulatory mechanism are complicated and unintelligible. In the current study, we newly identified the aquaporin 3 (AQP3) as a LUAD oncogenic factor with capacity to transport exogenous hydrogen peroxide (H₂ O₂ ) and increase intracellular ROS levels. Subsequently, we demonstrated that AQP3 was necessary for the facilitated diffusion of exogenous H₂ O₂ in LUAD cells and that the AQP3-dependent transport of H₂ O₂ accelerated cell growth and inhibited rapamycin-induced autophagy. Mechanistically, AQP3-mediated H₂ O₂ uptake increased intracellular ROS levels to inactivate PTEN and activate the AKT/mTOR pathway to subsequently inhibit autophagy and promote proliferation in LUAD cells. Finally, we suggested that AQP3 depletion retarded subcutaneous tumorigenesis in vivo and simultaneously decreased ROS levels and promoted autophagy. These findings underscore the importance of AQP3-induced oxidative stress in malignant transformation and suggest a therapeutic target for LUAD.

SUBMITTER: Wang Y 

PROVIDER: S-EPMC8353907 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature