Aerobic glycolysis: beyond proliferation

Abstract

Aerobic glycolysis has been generally associated with cancer cell proliferation, but fascinating and novel data show that it is also coupled to a series of further cellular functions. In this Mini Review, we will discuss some recent findings to illustrate newly defined roles for this process, in particular in non-malignant cells, supporting the idea that metabolism can be considered as an integral part of cellular signaling. Consequently, metabolism should be regarded as a plastic and highly dynamic determinant of a wide range of cellular specific functions.

Keywords: aerobic glycolysis; cellular signalling; immunometabolism; non-malignant cells; proliferation.

Figure 1

Schematic representation of the principal pathways involved in glucose catabolism summarizing recent findings discussed in the Mini Review (red boxes). (1) 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3 (PFKFB3) has a key role in regulating endothelial cells (ECs)sprouting; (2) switching to aerobic glycolysis is important for trained immunity in monocytes; (3) contact-inhibited fibroblasts rely on the pentose phosphate pathway (PPP) to produce NADPH; (4) GAPDH can function as an mRNA binding protein when not engaged in glycolysis, preventing the production of IFNγ; (5) succinate can act as intracellular signaling molecule, being involved in the production of IL-1β in BMDM; (6) Lactate secreted by cancer cells can act as extracellular signaling molecule, inducing the differentiation of macrophages into tumor-associated macrophages.