Regulation of cancer cell metabolism

Abstract

Interest in the topic of tumour metabolism has waxed and waned over the past century of cancer research. The early observations of Warburg and his contemporaries established that there are fundamental differences in the central metabolic pathways operating in malignant tissue. However, the initial hypotheses that were based on these observations proved inadequate to explain tumorigenesis, and the oncogene revolution pushed tumour metabolism to the margins of cancer research. In recent years, interest has been renewed as it has become clear that many of the signalling pathways that are affected by genetic mutations and the tumour microenvironment have a profound effect on core metabolism, making this topic once again one of the most intense areas of research in cancer biology.

Vacuolar ATPase as a potential therapeutic target and mediator of treatment resistance in cancer

“…Thus, cancer cell growth is often associated with a reprogramming of metabolism towards aerobic glycolysis. This is termed the Warburg effect and is associated with tumor hypoxia as well as activation of oncogenes, such as MYC and RAS, and inactivation of tumor suppressors, such as p53 65, 66, 67. This results in production of lactic acid and H + , and plasma membrane V‐ATPase may be key under these conditions for maintaining intracellular pH homeostasis 68.…”

Metabolic reprogramming of the tumor

“…Several recent reviews have considered particular aspects of the subject (Semenza, 2010;Berardi and Fantin, 2011;Brahimi-Horn et al, 2011;Cairns et al, 2011). The major bioenergetic pathways in cancer cells are summarized in Figure 1.…”

“…On the other hand, glutamine is transported into the cell and then to the mitochondria, where glutaminase converts it to glutamate; the latter is then converted to a-ketoglutarate, a TCAC intermediate. The relative flux increases refer to cancer cells in general in comparison with normal cells (see also Cairns et al, 2011). into glycolysis, allowing greater ATP production rates (Guppy et al, 1993). Furthermore, part of glucose-6-phosphate is shunted to the pentose phosphate pathway, generating ribose and NADPH, which sustain increased nucleic acid and fatty acid biosynthetic demands (Ramos-Montoya et al, 2006).…”

Functional screening identifies MCT4 as a key regulator of breast cancer cell metabolism and survival

“…Many solid tumours exhibit increased glucose uptake and lactate secretion, a feature known as the Warburg effect. Most metabolic alterations observed in cancer are the consequence of oncogene activation or inactivation of tumour suppressors [3], but genetic alterations in metabolic enzymes have also been observed. Cancer metabolism is a highly dynamic network that adapts to changes in environmental conditions.…”