RalA regulates ROS and ATP production in cancer cells by association with cavelolin-1
10.16156/j.1004-7220.2017.05.011
- VernacularTitle:RalA通过小窝蛋白-1调节肿瘤细胞活性氧自由基和三磷酸腺苷的生成
- Author:
Ying JIANG
1
;
Shun LI
;
Hong YANG
;
Chun-Hui WU
;
Yi-Yao LIU
Author Information
1. 电子科技大学生命科学与技术学院
- Keywords:
RalA;
Caveolin-1 (Cav-1);
Metabolism;
Mitochondria;
Reactive oxygen species (ROS)
- From:
Journal of Medical Biomechanics
2017;32(5):458-463
- CountryChina
- Language:Chinese
-
Abstract:
Objective By analyzing mitochondrial function,reactive oxygen species (ROS) and adenosine triphosphate (ATP) production under different levels of RalA and caveolin-1 (Cav-1) expression,to investigate the regulation role of RalA played in cancer metabolism and explore the possibility of its regulation role involved in Cav-1 and caveolae motility.Methods Firstly,RalA and Cav-1 expression were inhibited by siRNA in breast cancer cell line MDA-MB-231,and then the changes of mitochondrial membrane potential (MMP),ROS produc tion,ATP generation and L-lactate level before and after inhibition were assessed by Western blotting,confocal microscope and fluorescence quantification.Results (1) The decreased RalA and Cav-1 expression led to a significant reduction of MMP directly.(2) Low RalA and Cav-1 expression resulted in an inhibition of ATP production and an increase of H2O2 generation.With the reduction of MMP,mitochondrial malfunction was observed.(3) With mitochondrial function suppression,an elevated level of glycolysis metabolite L-lactate was also detected in RalA and Cav-1 deprived cells.Conclusions RalA and Cav-1 mediate cellular metabolic switch by inhibiting mitochondrial function and simultaneously boosting glycolysis.This regulation role of RalA depends on its association with Cav-1,and possibly is related to the endocytosis and motility of caveolae.The research findings enrich the cancer metabolic studies,and provide a novel approach for cancer therapeutic strategy targeted to cellular metabolism.
