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Published on: July 21, 2017
AQP3-mediated H2 O2 uptake inhibits LUAD autophagy by inactivating PTEN
Yawei Wang1,2, Di Chen2, Yu Liu1
1Department of Thoracic Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, China.
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.
Insights
Aquaporin 3 (AQP3) transports hydrogen peroxide into lung adenocarcinoma cells, increasing reactive oxygen species (ROS) and promoting cancer growth. Inhibiting AQP3 reduces ROS and tumor development, offering a potential therapeutic strategy.
Area of Science:
- Biochemistry
- Oncology
- Cell Biology
Background:
- Redox reprogramming is implicated in lung adenocarcinoma (LUAD) malignant transformation.
- The sources and signaling mechanisms of reactive oxygen species (ROS) in LUAD remain unclear.
Purpose of the Study:
- To identify novel oncogenic factors in LUAD.
- To elucidate the role of aquaporin 3 (AQP3) in LUAD pathogenesis and ROS regulation.
Main Methods:
- Investigated AQP3's role in transporting exogenous hydrogen peroxide (H2O2) in LUAD cells.
- Assessed the impact of AQP3 on cell proliferation, autophagy, and the PTEN/AKT/mTOR pathway.
- Evaluated the effect of AQP3 depletion on in vivo tumor growth.
Main Results:
- Identified AQP3 as a LUAD oncogenic factor facilitating H2O2 uptake and increasing intracellular ROS.
- Demonstrated that AQP3-dependent H2O2 transport promotes LUAD cell proliferation by inactivating PTEN and activating the AKT/mTOR pathway, thereby inhibiting autophagy.
- Showed that AQP3 depletion inhibits tumor growth in vivo, reduces ROS levels, and enhances autophagy.
Conclusions:
- AQP3 is a critical mediator of oxidative stress in LUAD, promoting malignant transformation.
- Targeting AQP3 represents a promising therapeutic strategy for lung adenocarcinoma.
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