Open AccessAQP3‐mediated H 2 O 2 uptake inhibits LUAD autophagy by inactivating PTEN
Author(s) -
Wang Yawei,
Chen Di,
Liu Yu,
Zhang Yong,
Duan Chao,
Otkur Wuxiyar,
Chen Huan,
Liu Xiaolong,
Xia Tian,
Qi Huan,
Piao Hailong,
Liu HongXu
Publication year - 2021
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.15008
Subject(s) - autophagy , aquaporin 3 , pi3k/akt/mtor pathway , pten , chemistry , microbiology and biotechnology , intracellular , carcinogenesis , reactive oxygen species , protein kinase b , cancer research , downregulation and upregulation , apoptosis , signal transduction , biology , biochemistry , aquaporin , gene
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 (H 2 O 2 ) and increase intracellular ROS levels. Subsequently, we demonstrated that AQP3 was necessary for the facilitated diffusion of exogenous H 2 O 2 in LUAD cells and that the AQP3‐dependent transport of H 2 O 2 accelerated cell growth and inhibited rapamycin‐induced autophagy. Mechanistically, AQP3‐mediated H 2 O 2 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.