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Property "Has-20abstract" (as page type) with input value "-5B-5BImage:MITOEAGLE-2Dlogo.jpg-7Cleft-7C100px-7Clink=http:-2F-2Fwww.mitoglobal.org-2Findex.php-2FMITOEAGLE-7CCOST-20Action-20MitoEAGLE-5D-5D-0ABladder-20cancer-20(BC)-20has-20a-20high-20incidence-20and-20recurrence-20rate.-20In-20addition,-20patients-20have-20a-20poor-20survival-20expectancy.-20Multiple-20signaling-20pathways-20that-20interact-20with-20mitochondria-20are-20involved-20in-20events-20related-20to-20tumor-20aggressiveness-20and-20growth.-20Thus,-20molecular-20classification-20and-20characterization-20of-20the-20tumor-20is-20pivotal-20to-20predict-20clinical-20outcomes,-20responses-20to-20chemotherapy-20and-20develop-20novel-20treatments.-20There-20are-20several-20targets-20towards-20personalized-20medicine,-20including-20mitochondrial-20DNA,-20mitochondrial-20metabolic-20enzymes-20and-20cellular-20signaling-20proteins.-20Among-20those,-20the-20mammalian-20target-20of-20rapamycin-20(mTOR)-20and-20NAD-2Ddependent-20deacetylase-20sirtuin-2D1-20(SIRT1)-20are-20known-20to-20independently-20mediate-20some-20cancer-20related-20features-20and-20mitochondria-20functioning.-20Herein-20we-20aimed-20to-20characterize-20how-20the-20activation-20or-20inhibition-20of-20SIRT1-20and-2For-20mTOR-20modulate-20the-20metabolic-20and-20bioenergetics-20profiles-20of-20highly-20proliferative-20and-20invasive-20stage-20IV-20BC-20cells.-20For-20that-20purpose,-20TCCSUP-20cells-20(BC-20stage-20IV)-20were-20cultured-20during-2024-20h-20in-20a-20normal-20media-20or-20supplemented-20with-20EX527-20(SIRT1-20inhibitor)-3B-20YK-2D3-2D237-20(SIRT1-20activator)-20and-20Rapamycin-20(mTOR-20inhibitor),-20as-20well-20as-20in-20a-20combined-20treatment-20of-20EX527+Rapamycin.-20In-20addition-20to-20cytotoxicity-20and-20migration-20tests,-20we-20determined-20the-20metabolic-20profile-20(metabolic-20fluxes,-201H-2DNMR),-20expression-20of-20membrane-20transporters-20(GLUT3-20and-20MCT1-2FMCT4,-20qPCR),-20mitochondrial-20potential-20(JC-2D1-20fluorescence),-20intact-20cell-20respirometry-20(Clark-2Dtype-20electrode)-20and-20mitochondrial-20copy-20number-20(qPCR)-20of-20the-20cells-20from-20each-20experimental-20group.-20Our-20results-20show-20that-20mTOR-20inhibition-20alone-20or-20in-20combination-20with-20SIRT1-20activation-20decreased-20cell-20density-20in-20BC-20cells.-20In-20addition,-20mitochondrial-20potential-20of-20BC-20cells-20was-20repressed-20after-20exposure-20to-20the-20combined-20treatment-20of-20mTOR-20inhibition-20with-20SIRT1-20activation-2Finhibition.-20In-20parallel-20with-20this,-20BC-20cells-20presented-20mitochondrial-20proton-20leak-20stimulation,-20with-20increased-20acetate-20consumption-20and-20decreased-20lactate-20production-20after-20the-20combined-20treatment-20with-20SIRT1-2FmTOR-20inhibitors.-20Interestingly,-20inhibition-20of-20mTOR-20alone-20upregulated-20the-20levels-20of-20transporters-20such-20as-20GLUT3-20and-20MCT4,-20but-20there-20was-20no-20direct-20action-20on-20the-20levels-20of-20metabolites-20transported-20by-20these-20transporters.-20On-20the-20other-20hand,-20activation-20of-20SIRT1-20downregulated-20the-20levels-20of-20MCT1-20but-20again,-20it-20did-20not-20affect-20lactate-20levels-20in-20the-20extracellular-20medium.-20Overall,-20our-20results-20show-20that-20the-20combined-20inhibition-20of-20mTOR-20and-20SIRT1-20in-20highly-20proliferative-20and-20invasive-20BC-20cells-20affects-20mitochondria-20physiology,-20which-20may-20elicit-20positive-20effects-20on-20the-20treatment-20of-20bladder-20cancer.-20Nevertheless,-20although-20our-20data-20shows-20promising-20results-20in-20the-20response-20of-20highly-20proliferative-20and-20invasive-20BC-20cells-20to-20the-20combined-20treatment-20with-20combined-20mTOR-20and-20SIRT1-20inhibitors,-20this-20is-20a-20first-20assessment-20of-20the-20metabolic-20and-20bioenergetics-20profile-20of-20these-20cells.-20Further-20studies-20will-20be-20needed-20to-20unveil-20the-20molecular-20mechanisms-20by-20which-20mitochondria-20mediates-20the-20positive-20response-20of-20highly-20proliferative-20and-20invasive-20BC-20cells-20to-20the-20combined-20inhibition-20of-20mTOR-20and-20SIRT1." contains invalid characters or is incomplete and therefore can cause unexpected results during a query or annotation process.

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