1. Academic Validation
  2. Cadmium induces cell growth in A549 and HELF cells via autophagy-dependent glycolysis

Cadmium induces cell growth in A549 and HELF cells via autophagy-dependent glycolysis

  • Toxicol In Vitro. 2020 Aug;66:104834. doi: 10.1016/j.tiv.2020.104834.
Xuan Wang 1 Zhiguo Li 1 Zeyun Gao 1 Qiujuan Li 1 Liping Jiang 1 Chengyan Geng 1 Xiaofeng Yao 1 Xiaoxia Shi 1 Yong Liu 2 Jun Cao 3
Affiliations

Affiliations

  • 1 Department of Occupational and Environmental Health, Dalian Medical University, No. 9 W. Lvshun South Road, Dalian 116044, China.
  • 2 School of Life Science and Medicine, Dalian University of Technology, Panjin 124221, China.
  • 3 Department of Occupational and Environmental Health, Dalian Medical University, No. 9 W. Lvshun South Road, Dalian 116044, China. Electronic address: caojunly@163.com.
Abstract

Cadmium (Cd) is a pervasive harmful metal in the environment. It is a well-known inducer of tumorigenesis, but its mechanism is still unclear. We have previously reported that Cd-induced Autophagy was apoptosis-dependent and prevents apoptotic cell death to ensure the growth of A549 cells. In this study, the mechanism was further investigated. Cd treatment increased glucose uptake and lactate release significantly. Meanwhile, the protein level of GLUT1,HKII,PKM2 and LDHA increased in a time-dependent manner, indicating that Cd induced aerobic glycolysis in A549 and HELF cells. The inhibitors of Autophagy, 3MA, and CQ, repressed Cd-induced glycolysis-related proteins, indicating that Autophagy was involved in Cd-induced glycolysis in A549 and HELF cells. Knockdown of ATG4B or ATG5 by siATG4B and siATG5 decreased Cd-induced glycolysis, while overexpression of ATG4B enhanced glycolysis. These results demonstrated that Cd-induced glycolysis was autophagy-dependent. Then, glycolysis inhibitor, 2DG and siPKM2 could inhibit Cd-induced cell viability and cell cycle progression compared to only Cd treatment, indicating that glycolysis played an important role in Cd-induced cell growth. Finally, co-treatment of transfection of ATG4B-DNA plasmids with 2DG or siPKM2 further demonstrated that the autophagy-glycolysis axis played an important role in Cd-induced cell cycle progression. Taken together, our results suggested that Cd-induced glycolysis is autophagy-dependent and the autophagy-glycolysis axis underlies the mechanism of Cd-induced cell growth in A549 and HELF cells.

Keywords

Autophagy; Cadmium; Cell cycle; Glycolysis.

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