Oxidative Pentose Phosphate Pathway Enzyme 6-Phosphogluconate Dehydrogenase Plays a Key Role in Breast Cancer Metabolism

Biology

Jordi Perarnau¹  Marta Cascante¹  Adrian Benito¹  IbrahimH. Polat¹  Roldán Cortés¹  Rohit Bharat¹  Míriam Tarrado-Castellarnau¹  Philippe Sabatier² 

[1] Department of Biochemistry and Molecular Biomedicine and Institute of Biomedicine (IBUB), Faculty of Biology, Universitat de Barcelona, Av Diagonal 643, 08028 Barcelona, Spain;Equipe Environnement et Prédiction de la Santé des Populations, Laboratoire TIMC (UMR 5525), CHU de Grenoble, Université Grenoble Alpes, 38700 CEDEX La Tronche, France;

关键词: breast cancer;    pentose phosphate pathway;    cancer metabolism;    6PGD;   

DOI  :  10.3390/biology10020085

来源: DOAJ

【 摘 要 】

The pentose phosphate pathway (PPP) plays an essential role in the metabolism of breast cancer cells for the management of oxidative stress and the synthesis of nucleotides. 6-phosphogluconate dehydrogenase (6PGD) is one of the key enzymes of the oxidative branch of PPP and is involved in nucleotide biosynthesis and redox maintenance status. Here, we aimed to analyze the functional importance of 6PGD in a breast cancer cell model. Inhibition of 6PGD in MCF7 reduced cell proliferation and showed a significant decrease in glucose consumption and an increase in glutamine consumption, resulting in an important alteration in the metabolism of these cells. No difference in reactive oxygen species (ROS) production levels was observed after 6PGD inhibition, indicating that 6PGD, in contrast to glucose 6-phosphate dehydrogenase, is not involved in redox balance. We found that 6PGD inhibition also altered the stem cell characteristics and mammosphere formation capabilities of MCF7 cells, opening new avenues to prevent cancer recurrance after surgery or chemotherapy. Moreover, inhibition of 6PGD via chemical inhibitor S3 resulted in an induction of senescence, which, together with the cell cycle arrest and apoptosis induction, might be orchestrated by p53 activation. Therefore, we postulate 6PGD as a novel therapeutic target to treat breast cancer.

【 授权许可】

Unknown