Metabolic and OXPHOS Activities Quantified by Temporal ex vivo Analysis Display Patient-Specific Metabolic Vulnerabilities in Human Breast Cancers.

作者: Andre Koit , Natalja Timohhina , Laura Truu , Vladimir Chekulayev , Shivakumar Gudlawar

DOI: 10.3389/FONC.2020.01053

关键词:

摘要: Research on mitochondrial metabolism and respiration are rapidly developing areas, however, efficient widely accepted methods for studying these in solid tumors still missing. Here, we developed a new method without isotope tracing to quantitate time dependent citrate efflux cell lines human breast cancer samples. In addition, studied ADP-activated both of the sample types using selective permeabilization showed that metabolic activity not equally linked. Three times lower amount mitochondria scarcely respiring MDA-MB-231 cells convert pyruvate glutamate into at 20% higher rate than highly MCF-7 do. Surprisingly, analysis 59 cancers revealed opposite clinical samples as aggressive subtypes, comparison less presented with rate. Additionally, substrate preference (pyruvate or glutamate) triple negative probable causes high glutamine dependence this subtype reasons why some able overcome glutaminase inhibition. Our research concludes two used fail replicate function seen respective And finally, easy described here, where small molecule analyzed together, can increase success translational ultimately benefit patients cancer.

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