2-Deoxyglucose induces the expression of thioredoxin interacting protein (TXNIP) by increasing O-GlcNAcylation - Implications for targeting the Warburg effect in cancer cells

Biochemical and Biophysical Research Communications
Shin Yee Hong, Thilo Hagen

Abstract

The high proliferation rate of cancer cells and the microenvironment in the tumor tissue require the reprogramming of tumor cell metabolism. The major mechanism of metabolic reprogramming in cancer cells is the Warburg effect, defined as the preferential utilization of glucose via glycolysis even in the presence of oxygen. Targeting the Warburg effect is considered as a promising therapeutic strategy in cancer therapy. In this regard, the glycolytic inhibitor 2-deoxyglucose (2DG) has been evaluated clinically. 2DG exerts its effect by directly inhibiting glycolysis at the level of hexokinase and phosphoglucoisomerase. In addition, 2DG is also known to induce the expression of thioredoxin interacting protein (TXNIP), a tumor suppressor protein and an important negative regulator of cellular glucose uptake. Hence, characterization of the mechanism through which 2DG regulates TXNIP expression may reveal novel approaches to target the Warburg effect in cancer cells. Therefore, in this study we sought to test various hypotheses for the mechanistic basis of the 2DG dependent TXNIP regulation. We have shown that 2DG induced TXNIP expression is independent of carbohydrate response element mediated transcription. Furthermore, the induct...Continue Reading

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Citations

Jan 18, 2018·Proceedings of the National Academy of Sciences of the United States of America·Karthik NagarajHaim Werner
Jan 15, 2020·American Journal of Physiology. Endocrinology and Metabolism·XiaoLong JiangHuaBin Zhu
Dec 10, 2016·Psychopharmacology·Yury S TarahovskyNadezhda M Zakharova
Jun 6, 2020·Cells·Sher Bahadur PoudelShoshana Yakar
Nov 8, 2020·Cell Stress & Chaperones·Yang LiuShi-Ze Li
May 26, 2017·Molecular Cancer Research : MCR·Kazumasa Moriwaki, Michio Asahi
Jan 29, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Huan GaoYanqing Song

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