Serine, glycine and one-carbon units: cancer metabolism in full circle

Abstract

One carbon metabolism involving the folate and methionine cycle integrates carbon units from amino acids, including serine and glycine, and generates diverse outputs, such as the biosynthesis of lipids, nucleotides and proteins, the maintenance of redox status, and the substrates for methylation reactions. Long considered a ‘housekeeping’ process, this pathway has been recently shown to have additional complexity. Recent genetic and functional evidence also suggests that hyperactivation of this pathway is a possible driver of oncogenesis and establishes links to cellular epigenetic status. Given the wealth of clinically available agents that target one carbon metabolism, these new findings could present opportunities for translation into precision cancer medicine.

Cancer metabolism in space and time: Beyond the Warburg effect

“…De spite to day's vi brant re search on can cer me tab o lism and the high po ten tial of this field for can cer ther apy, the next years will be cru cial for un der stand ing the cur rent con tri bu tion of re search on tu mor me tab o lism to the de vel op ment of novel treat ments. While an timeta bolic drugs have been his tor i cally one of the first ap proved chemother apy [271], and that sev eral drugs have fur ther shown an ac tiv ity on meta bolic path ways [272], spe cific ther a pies are still miss ing to tar get can cer me tab o lism per se. In deed, while there is a con sen sus on the fact that can cer me tab o lism dif fers from that of nor mal cells, it is not yet firmly es tab lished how to tar get this dif fer ence ef fec tively [273].…”

Hepatocellular carcinoma redirects to ketolysis for progression under nutrition deprivation stress

“…Since nutrient-limiting conditions are not uncommon during cancer development [40], we are interested in what pathways or which fuels might provide alternative sources for energy production in starved cancer cells. Using a screening approach to determine changes of lipid metabolism-related gene expression induced by nutrition stresses, we have discovered that the expression level of OXCT1, a key enzyme for ketone body catabolism, is dramatically increased in serum-starved liver cancer cells ( Figure 1A and 1B).…”

Creatine: a miserable life without it

“…In addition, inflammatory parameters including TNF-a, C-reactive protein and IL-6, as well as markers for oxidative damage, were all lowered. The fact that creatine supplementation restored the impaired creatine-CK system in tumor cells led the authors to surmise that inhibition of AGAT and/or GAMT, which is thought to support cancer cell metabolism by contributing to polyamine and methionine synthesis, as shown by Locasale (2013), may be one of the reasons for the anti-cancer effects of creatine. The data reported by Campos Ferraz et al (2016) are in accord with similar data by Patra et al (2008), and suggest a potential therapeutic effect of creatine for the treatment of cancer (Pal et al 2016).…”