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Metabolic reprogramming in triple-negative breast cancer through Myc suppression of TXNIP

2015; National Academy of Sciences; Volume: 112; Issue: 17 Linguagem: Inglês

10.1073/pnas.1501555112

1091-6490

Liangliang Shen, John O'shea, Mohan R. Kaadige, Stéphanie Cunha, Blake R. Wilde, Adam L. Cohen, Alana L. Welm, Donald E. Ayer,

Mitochondrial Function and Pathology

Significance Triple-negative breast cancers (TNBCs) are aggressive with poor clinical outcomes. Understanding the pathways that control their aggressive growth may reveal new targets for therapeutic intervention. TNBCs are highly glycolytic, providing fuel for growth promoting biosynthetic pathways. We establish that the c-Myc transcription factor drives this metabolic phenotype. Classically, the c-Myc proto-oncogene drives glycolysis by activating target genes encoding glycolytic enzymes and glucose transporters; however, we show here that c-Myc represses the expression of thioredoxin-interacting protein (TXNIP), which is a potent blocker of glucose utilization. Thus, c-Myc’s repression of TXNIP provides an additional route to c-Myc–driven glucose metabolism. Highlighting the clinical significance of our finding, a Myc high /TXNIP low gene signature correlates with poor overall survival in TNBC but not in other subclasses of breast cancer.