title: Transferrin receptor regulates pancreatic cancer growth by modulating mitochondrial respiration and ROS generation.
abstract: The transferrin receptor (TfR1) is upregulated in malignant cells and its expression is associated with cancer progression. Because of its pre-eminent role in cell proliferation, TfR1 has been an important target for the development of cancer therapy. Although TfR1 is highly expressed in pancreatic cancers, what it carries out in these refractory cancers remains poorly understood. Here we report that TfR1 supports mitochondrial respiration and ROS production in human pancreatic ductal adenocarcinoma (PDAC) cells, which is required for their tumorigenic growth. Elevated TfR1 expression in PDAC cells contributes to oxidative phosphorylation, which allows for the generation of ROS. Importantly, mitochondrial-derived ROS are essential for PDAC growth. However, exogenous iron supplement cannot rescue the defects caused by TfR1 knockdown. Moreover, we found that TfR1 expression determines PDAC cells sensitivity to oxidative stress. Together, our findings reveal that TfR1 can contribute to the mitochondrial respiration and ROS production, which have essential roles in growth and survival of pancreatic cancer.
authors: Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul 137-701, South Korea; Institute for Aging and Metabolic Diseases, College of Medicine, The Catholic University of Korea, Seoul 137-701, South Korea. Electronic address: smjeong@catholic.ac.kr.
authors: Seung Min
authors: SM
authors: Jeong
authors: School of Biological Sciences and Institute of Molecular Biology and Genetics, Seoul National University, Seoul 151-742, South Korea.
authors: Sunsook
authors: S
authors: Hwang
authors: School of Biological Sciences and Institute of Molecular Biology and Genetics, Seoul National University, Seoul 151-742, South Korea.
authors: Rho Hyun
authors: RH
authors: Seong
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D011990:Receptors, Transferrin / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; C068126:CD71 antigen; D017382:Reactive Oxygen Species; D011990:Receptors, Transferrin; D010100:Oxygen
keywords: Mitochondrial respiration; PDAC; ROS; Transferrin receptor