Yin and Yang of YY1 regulation on tumor metabolic reprogramming

Abstract Metabolism is the foundation of all cellular biological activities. A proliferating cell not only performs catabolic processes to support cellular bioenergetics but also performs anabolic biomass accumulation for cell proliferation. Throughout the course of tumorigenesis, tumor accumulates mutations in oncogenes and tumor suppressor genes, causing alterations to intracellular signaling pathways and further affecting cell metabolism. Currently known as one of the hallmarks of cancer, tumor metabolic reprogramming alters catabolism, anabolism, and redox balance to meet the bioenergetic, biosynthetic, and homeostatic demands of malignant cells. Due to its basic, important roles in tumorigenesis, targeting tumor metabolism has emerged as a promising strategy for treating cancer. Based on past and recent findings, in this chapter, we provide a conceptual perspective on how a multifunctional protein Yin Yang 1 (YY1) directly and indirectly influences multiple pathways in tumor metabolic reprogramming. YY1 controls the glycolytic flux in the catabolic pathway by regulating the glucose uptake rate and the expression of glycolytic enzymes, providing energy to support tumor growth. YY1 controls and directs the anabolic pathway toward the biosynthesis of molecules needed for the formation of new daughter cells, including the increase of the pentose phosphate pathway–derived nucleotide precursors and lipid for building cell membranes, as well as mitochondrial biogenesis. Finally, YY1 could affect the response to antitumor therapy by regulating the redox homeostasis. Understanding these concepts will support the development of new approaches to target tumor metabolism based on YY1 inhibition.