Search results for "MCL1"

showing 3 items of 3 documents

MYC and MCL1 Cooperatively Promote Chemotherapy-Resistant Breast Cancer Stem Cells via Regulation of Mitochondrial Oxidative Phosphorylation

2017

Summary Most patients with advanced triple-negative breast cancer (TNBC) develop drug resistance. MYC and MCL1 are frequently co-amplified in drug-resistant TNBC after neoadjuvant chemotherapy. Herein, we demonstrate that MYC and MCL1 cooperate in the maintenance of chemotherapy-resistant cancer stem cells (CSCs) in TNBC. MYC and MCL1 increased mitochondrial oxidative phosphorylation (mtOXPHOS) and the generation of reactive oxygen species (ROS), processes involved in maintenance of CSCs. A mutant of MCL1 that cannot localize in mitochondria reduced mtOXPHOS, ROS levels, and drug-resistant CSCs without affecting the anti-apoptotic function of MCL1. Increased levels of ROS, a by-product of a…

0301 basic medicinePhysiologyMice NudeTriple Negative Breast NeoplasmsOxidative phosphorylationTumor initiationMitochondrionBiologyOxidative PhosphorylationArticleProto-Oncogene Proteins c-myc03 medical and health sciencesCancer stem cellCell Line TumorAnimalsHumansMCL1Molecular BiologyTriple-negative breast cancerchemistry.chemical_classificationReactive oxygen speciesCell BiologyMitochondria030104 developmental biologychemistryDrug Resistance NeoplasmNeoplastic Stem CellsCancer researchMyeloid Cell Leukemia Sequence 1 ProteinFemaleStem cellReactive Oxygen SpeciesCell Metabolism
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Loss of MCL1 function sensitizes the MDA-MB-231 breast cancer cells to rh-TRAIL by increasing DR4 levels.

2019

Triple-negative breast cancer (TNBC) is a form of BC characterized by high aggressiveness and therapy resistance probably determined by cancer stem cells. MCL1 is an antiapoptotic Bcl-2 family member that could limit the efficacy of anticancer agents as recombinant human tumor necrosis factor related apoptosis-inducing ligand (rh-TRAIL). Here, we investigated MCL1 expression in TNBC tissues and cells. We found MCL1 differentially expressed (upregulated or downregulated) in TNBC tissues. Furthermore, in comparison to the human mammary epithelial cells, we found that MDA-MB-231 cells show similar messenger RNA levels but higher MCL1 protein levels, whereas it resulted downregulated in MDA-MB-…

0301 basic medicinecancer stem cellIndolesPhysiologyCell SurvivalClinical BiochemistryCellPopulationApoptosisTNF-Related Apoptosis-Inducing Ligand03 medical and health sciences0302 clinical medicineCancer stem cellSettore BIO/10 - BiochimicaCell Line Tumormedicinerh-TRAILBiomarkers TumorGene silencingHumansViability assayGene SilencingeducationCell ShapeCell ProliferationMembrane Potential Mitochondrialeducation.field_of_studySulfonamidesChemistryCell growthCell CycleCell BiologyCell cycleRecombinant ProteinsGene Expression Regulation NeoplasticReceptors TNF-Related Apoptosis-Inducing Ligand030104 developmental biologymedicine.anatomical_structureMCL1ApoptosisDR4 receptor030220 oncology & carcinogenesisCancer researchtriple-negative breast cancerMyeloid Cell Leukemia Sequence 1 ProteinJournal of cellular physiology
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NKG2D induces Mcl-1 expression and mediates survival of CD8 memory T cell precursors via phosphatidylinositol 3-kinase.

2013

Abstract Memory formation of activated CD8 T cells is the result of a specific combination of signals that promote long-term survival and inhibit differentiation into effector cells. Much is known about initial cues that drive memory formation, but it is poorly understood which signals are essential during the intermediate stages before terminal differentiation. NKG2D is an activating coreceptor on Ag-experienced CD8 T cells that promotes effector cell functions. Its role in memory formation is currently unknown. In this study, we show that NKG2D controls formation of CD8 memory T cells by promoting survival of precursor cells. We demonstrate that NKG2D enhances IL-15–mediated PI3K signalin…

Cell SurvivalImmunologyCytomegalovirusBiologyCD8-Positive T-LymphocytesLymphocyte ActivationMiceMemory cellPrecursor cellmedicineImmunology and AllergyCytotoxic T cellAnimalsIL-2 receptorReceptors ImmunologicInterleukin-15Mice KnockoutPrecursor Cells T-LymphoidNK cells; NKG2D; CD8 T cellsEffectorCell DifferentiationNKG2DNKG2D; CD8 T cell memory; Mcl1; PI3KCell biologyMice Inbred C57BLmedicine.anatomical_structureProto-Oncogene Proteins c-bcl-2NK Cell Lectin-Like Receptor Subfamily KCytomegalovirus InfectionsMyeloid Cell Leukemia Sequence 1 ProteinPhosphatidylinositol 3-KinaseMemory T cellImmunologic MemoryCD8Signal TransductionJournal of immunology (Baltimore, Md. : 1950)
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