Biomol Ther.  2018 Jan;26(1):29-38. 10.4062/biomolther.2017.179.

The Pentose Phosphate Pathway as a Potential Target for Cancer Therapy

• Cho ES
• Cha YH
• Kim HS
• Kim NH
• Yook JI

• KMID: 2400812
• DOI: http://doi.org/10.4062/biomolther.2017.179

Abstract

During cancer progression, cancer cells are repeatedly exposed to metabolic stress conditions in a resource-limited environment which they must escape. Increasing evidence indicates the importance of nicotinamide adenine dinucleotide phosphate (NADPH) homeostasis in the survival of cancer cells under metabolic stress conditions, such as metabolic resource limitation and therapeutic intervention. NADPH is essential for scavenging of reactive oxygen species (ROS) mainly derived from oxidative phosphorylation required for ATP generation. Thus, metabolic reprogramming of NADPH homeostasis is an important step in cancer progression as well as in combinational therapeutic approaches. In mammalian, the pentose phosphate pathway (PPP) and one-carbon metabolism are major sources of NADPH production. In this review, we focus on the importance of glucose flux control towards PPP regulated by oncogenic pathways and the potential therein for metabolic targeting as a cancer therapy. We also summarize the role of Snail (Snai1), an important regulator of the epithelial mesenchymal transition (EMT), in controlling glucose flux towards PPP and thus potentiating cancer cell survival under oxidative and metabolic stress.

Keyword

Pentose phosphate pathway; NADPH; Glucose-6-phosphate dehydrogenase; Snail; Epithelial-mesenchymal transition

MeSH Terms

Adenosine Triphosphate
Cell Survival
Epithelial-Mesenchymal Transition
Glucose
Glucosephosphate Dehydrogenase
Homeostasis
Metabolism
NADP
Oxidative Phosphorylation
Pentose Phosphate Pathway*
Reactive Oxygen Species
Snails
Stress, Physiological
United Nations
Adenosine Triphosphate
Glucose
Glucosephosphate Dehydrogenase
NADP
Reactive Oxygen Species