The following is a summary of “Serine synthesis and catabolism in starved lung cancer and primary bronchial epithelial cells,” published in the March 2024 issue of Oncology by Haitzmann et al.
Serine and glycine play crucial roles as building blocks in the proliferation of cells, with their availability impacting various cellular processes. While lung cancer cells exhibit diverse expression patterns of serine synthesis genes, the presence of the key enzyme phosphoglycerate dehydrogenase (PHGDH) has been linked to unfavorable prognostic outcomes. Despite this, the influence of glucose deprivation, commonly encountered in solid cancers, on serine metabolism remains poorly understood. Here, the researchers employed stable isotopic tracing methods to investigate serine and glycine synthesis pathways in different lung cancer cell lines and normal bronchial epithelial cells under varying serine, glycine, and glucose conditions.
Surprisingly, the study group observed that low glucose levels (0.2 mM, 3–5% of normal plasma levels) did not hinder but maintained or even stimulated de novo serine synthesis. Additionally, gluconeogenesis from glutamine was found to contribute carbon sources to serine and glycine synthesis under low glucose conditions. Moreover, low glucose treatment consistently promoted the conversion of serine to glycine, accompanied by increased expression of mitochondrial one-carbon metabolism enzymes, including serine hydroxymethyltransferase (SHMT2) and methylenetetrahydrofolate dehydrogenase (MTHFD2). Furthermore, investigators noted a significant rise in the relative contribution of de novo serine synthesis under low serine/glycine conditions. Similar metabolic adaptations were observed in bronchial epithelial cells, albeit with lower levels of serine synthesis and serine-to-glycine conversion compared to PHGDH-positive cancer cells.
In conclusion, their findings underscore the dynamic interplay between glucose and non-glucose carbon sources in regulating serine and glycine metabolism, highlighting the remarkable adaptability of the downstream one-carbon metabolism pathway to fluctuating glucose availability.
Source: cancerandmetabolism.biomedcentral.com/articles/10.1186/s40170-024-00337-3