GPx1 is involved in the induction of protective autophagy in pancreatic cancer cells in response to glucose deprivation.

Abstract

Given the dense stroma and poor vascularization, access to nutrients is limited in the microenvironment of pancreatic ductal adenocarcinoma (PDA). PDA cells can efficiently recycle various metabolic substrates through the activation of different rescuing pathways, including the autophagy pathway. However, the precise roles of autophagy in cancer metabolism are not yet fully understood. In the present study, we first monitored the effect of glucose deprivation on autophagy and on the expression of glutathione peroxidase-1 (GPx1) in PDA cells under the glucose-free environment. Glucose starvation induced progressive autophagy activation in PDA cells via the activation of ROS/AMPK signaling. GPx1 degradation caused by glucose deprivation led to further ROS-dependent autophagy activation. Both GPx1 overexpression and autophagy inhibition sensitized cells to starvation-induced cell death through the activation of caspase-dependent apoptosis. Moreover, GPx1 may regulate glycolysis inhibition in PDA cells under glucose-deprived conditions. In summary, this study increases our understanding of the role of GPx1 in the induction of protective autophagy in PDA cells under extreme glucose starvation and may provide new therapeutic targets or innovative therapies.

• Authors: Qingcai Meng, Jin Xu, Chen Liang, Jiang Liu, Jie Hua, Yiyin Zhang, Quanxing Ni, Si Shi, Xianjun Yu
• Journal: Cell death & disease (Cell Death Dis) Vol. 9 Issue 12 Pg. 1187 (12 11 2018) ISSN: 2041-4889 [Electronic] England
• PMID: 30538220 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glutathione Peroxidase
• Glucose
• Glutathione Peroxidase GPX1
• GPX1 protein, human

Topics

• Adenocarcinoma (genetics, metabolism, pathology)
• Apoptosis (genetics)
• Autophagy (genetics)
• Carcinoma, Pancreatic Ductal (genetics, metabolism, pathology)
• Cell Line, Tumor
• Female
• Gene Expression Regulation, Neoplastic (genetics)
• Glucose (metabolism)
• Glutathione Peroxidase (genetics)
• Humans
• Male
• Pancreas (metabolism, pathology)
• Signal Transduction
• Starvation (genetics, pathology)
• Glutathione Peroxidase GPX1