ABSTRACT
Mitochondrial dysregulation plays a central role in cancers and drives reactive oxygen species (ROS)-dependent tumor progression. We investigated the pro-tumoral roles of mitochondrial dynamics and altered intracellular ROS levels in pancreatic ductal adenocarcinoma (PDAC). We identified 'family with sequence similarity 49 member B' (FAM49B) as a mitochondria-localized protein that regulates mitochondrial fission and cancer progression. Silencing FAM49B in PDAC cells resulted in increased fission and mitochondrial ROS generation, which enhanced PDAC cell proliferation and invasion. Notably, FAM49B expression levels in PDAC cells were downregulated by the tumor microenvironment. Overall, the results of this study show that FAM49B acts as a suppressor of cancer cell proliferation and invasion in PDAC by regulating tumor mitochondrial redox reactions and metabolism.
Subject(s)
Adenocarcinoma/secondary , Biomarkers, Tumor/metabolism , Carcinoma, Pancreatic Ductal/secondary , Gene Expression Regulation, Neoplastic , Intracellular Signaling Peptides and Proteins/metabolism , Mitochondria/pathology , Mitochondrial Proteins/metabolism , Neoplasm Proteins/metabolism , Pancreatic Neoplasms/pathology , Reactive Oxygen Species/metabolism , Adenocarcinoma/genetics , Adenocarcinoma/metabolism , Animals , Apoptosis , Biomarkers, Tumor/genetics , Carcinoma, Pancreatic Ductal/genetics , Carcinoma, Pancreatic Ductal/metabolism , Cell Movement , Cell Proliferation , Humans , Intracellular Signaling Peptides and Proteins/genetics , Mice , Mice, Inbred NOD , Mice, SCID , Mitochondria/metabolism , Mitochondrial Proteins/genetics , Neoplasm Proteins/genetics , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/metabolism , Prognosis , Tumor Cells, Cultured , Xenograft Model Antitumor Assays , Pancreatic NeoplasmsABSTRACT
PIP: The author develops a model for assessing the effect of changes in the age-specific death rate on life expectancy. The model is illustrated using data for Bulgaria for the period 1900-1980. (SUMMARY IN ENG AND RUS)^ieng
Subject(s)
Life Expectancy , Models, Theoretical , Mortality , Bulgaria , Demography , Developed Countries , Europe , Europe, Eastern , Longevity , Population , Population Dynamics , ResearchABSTRACT
PIP: Determinants of changes in endogenous and exogenous infant mortality rates in Bulgaria are analyzed for the period 1947-1981. Mortality is studied by sex and by town or village. Factors contributing to excess male mortality are considered. (summary in ENG, RUS)^ieng
