首页|Aberrant LETM1 elevation dysregulates mitochondrial functions and energy metabolism and promotes lung metastasis in osteosarcoma
Aberrant LETM1 elevation dysregulates mitochondrial functions and energy metabolism and promotes lung metastasis in osteosarcoma
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Osteosarcoma is a differentiation-deficient disease,and despite the unique advan-tages and great potential of differentiation therapy,there are only a few known differentia-tion inducers,and little research has been done on their targets.Cell differentiation is associated with an increase in mitochondrial content and activity.The metabolism of some tu-mor cells is characterized by impaired oxidative phosphorylation,as well as up-regulation of aerobic glycolysis and pentose phosphate pathways.Leucine-containing zipper and EF-hand transmembrane protein 1(LETM1)is involved in the maintenance of mitochondrial morphology and is closely associated with tumorigenesis and progression,as well as cancer cell stemness.We found that MG63 and 143B osteosarcoma cells overexpress LETM1 and exhibit abnormalities in mitochondrial structure and function.Knockdown of LETM1 partially restored the mitochon-drial structure and function,inhibited the pentose phosphate pathway,promoted oxidative phosphorylation,and led to osteogenic differentiation.It also inhibited spheroid cell forma-tion,proliferation,migration,and invasion in an in vitro model.When LETM1 was knocked down in vivo,there was reduced tumor formation and lung metastasis.These data suggest that mitochondria are aberrant in LETM1-overexpressing osteosarcoma cells,and knockdown of LETM1 partially restores the mitochondrial structure and function,inhibits the pentose phosphate pathway,promotes oxidative phosphorylation,and increases osteogenic differenti-ation,thereby reducing malignant biological behavior of the cells.
Cancer metabolismDifferentiationLETM1OsteosarcomaStemness
Yulu Shi、Quan Kang、Hong Zhou、Xiaohan Yue、Yang Bi、Qing Luo
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Stem Cell Biology and Therapy Laboratory,The Children's Hospital of Chongqing Medical University,National Clinical Research Center for Child Health and Disorders,Ministry of Education Key Laboratory of Child Development and Disorders,Chongqing Key Laboratory of Pediatrics,Chongqing 400014,China
Department of Pediatric Surgery,The Children's Hospital of Chongqing Medical University,Chongqing 400014,China
国家自然科学基金Chongqing Science and Technology Commission,China
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