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

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

Content Provider	MDPI
Author	Rold, án Cortés Polat, Ibrahim H. Tarrado-Castellarnau, Míriam Perarnau, Jordi Benito, Adrian Sabatier, Philippe Cascante, Marta
Copyright Year	2021
Description	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.
Starting Page	85
e-ISSN	20797737
DOI	10.3390/biology10020085
Journal	Biology
Issue Number	2
Volume Number	10
Language	English
Publisher	MDPI
Publisher Date	2021-01-23
Access Restriction	Open
Subject Keyword	Biology Biochemistry and Molecular Biology Breast Cancer Pentose Phosphate Pathway Cancer Metabolism 6pgd
Content Type	Text
Resource Type	Article

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