Frontiers in Cell and Developmental Biology (Feb 2022)
PPARγ/SOD2 Protects Against Mitochondrial ROS-Dependent Apoptosis via Inhibiting ATG4D-Mediated Mitophagy to Promote Pancreatic Cancer Proliferation
- Shuang Nie,
- Shuang Nie,
- Zhao Shi,
- Zhao Shi,
- Mengyue Shi,
- Mengyue Shi,
- Hongzhen Li,
- Hongzhen Li,
- Xuetian Qian,
- Xuetian Qian,
- Chunyan Peng,
- Chunyan Peng,
- Xiwei Ding,
- Xiwei Ding,
- Shu Zhang,
- Shu Zhang,
- Ying Lv,
- Ying Lv,
- Ying Lv,
- Lei Wang,
- Lei Wang,
- Lei Wang,
- Bo Kong,
- Bo Kong,
- Bo Kong,
- Xiaoping Zou,
- Xiaoping Zou,
- Xiaoping Zou,
- Shanshan Shen,
- Shanshan Shen,
- Shanshan Shen
Affiliations
- Shuang Nie
- Department of Gastroenterology, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
- Shuang Nie
- Nanjing University Institute of Pancreatology, Nanjing, China
- Zhao Shi
- Nanjing University Institute of Pancreatology, Nanjing, China
- Zhao Shi
- Department of Gastroenterology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, China
- Mengyue Shi
- Department of Gastroenterology, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
- Mengyue Shi
- Nanjing University Institute of Pancreatology, Nanjing, China
- Hongzhen Li
- Department of Gastroenterology, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
- Hongzhen Li
- Nanjing University Institute of Pancreatology, Nanjing, China
- Xuetian Qian
- Nanjing University Institute of Pancreatology, Nanjing, China
- Xuetian Qian
- Department of Gastroenterology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, China
- Chunyan Peng
- Department of Gastroenterology, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
- Chunyan Peng
- Nanjing University Institute of Pancreatology, Nanjing, China
- Xiwei Ding
- Department of Gastroenterology, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
- Xiwei Ding
- Nanjing University Institute of Pancreatology, Nanjing, China
- Shu Zhang
- Department of Gastroenterology, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
- Shu Zhang
- Nanjing University Institute of Pancreatology, Nanjing, China
- Ying Lv
- Department of Gastroenterology, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
- Ying Lv
- Nanjing University Institute of Pancreatology, Nanjing, China
- Ying Lv
- Department of Gastroenterology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, China
- Lei Wang
- Department of Gastroenterology, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
- Lei Wang
- Nanjing University Institute of Pancreatology, Nanjing, China
- Lei Wang
- Department of Gastroenterology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, China
- Bo Kong
- Department of Gastroenterology, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
- Bo Kong
- Nanjing University Institute of Pancreatology, Nanjing, China
- Bo Kong
- Department of Surgery, Ulm University Hospital, Ulm University, Ulm, Germany
- Xiaoping Zou
- Department of Gastroenterology, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
- Xiaoping Zou
- Nanjing University Institute of Pancreatology, Nanjing, China
- Xiaoping Zou
- Department of Gastroenterology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, China
- Shanshan Shen
- Department of Gastroenterology, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
- Shanshan Shen
- Nanjing University Institute of Pancreatology, Nanjing, China
- Shanshan Shen
- Department of Gastroenterology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, China
- DOI
- https://doi.org/10.3389/fcell.2021.745554
- Journal volume & issue
-
Vol. 9
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive disease with poor prognosis. Our previous study found that peroxisome proliferator activated receptor gamma (PPARγ) was capable of enhancing glycolysis in PDAC cells. However, whether PPARγ could promote PDAC progression remains unclear. In our present study, PPARγ was positively associated with tumor size and poor prognosis in PDAC patients. Functional assays demonstrated that PPARγ could promote the proliferation of pancreatic cancer cells in vitro and in vivo. Additionally, flow cytometry results showed that PPARγ decreased mitochondrial reactive oxygen species (mitochondrial ROS) production, stabilized mitochondrial membrane potential (MMP) and inhibited cell apoptosis via up-regulating superoxide dismutase 2 (SOD2), followed by the inhibition of ATG4D-mediated mitophagy. Meanwhile, the activation of PPARγ might reduce pancreatic cancer cell stemness to improve PDAC chemosensitivity via down-regulating ATG4D. Thus, these results revealed that PPARγ/SOD2 might protect against mitochondrial ROS-dependent apoptosis via inhibiting ATG4D-mediated mitophagy to promote pancreatic cancer proliferation, further improving PDAC chemosensitivity.
Keywords
