De novo serine biosynthesis from glucose predicts sex-specific response to antifolates in non-small cell lung cancer cell lines.

ABSTRACT: Lung cancer is the leading cause of cancer-related death. Intriguingly, males with non-small cell lung cancer (NSCLC) have a higher mortality rate than females. Here, we investigated the role of serine metabolism as a predictive marker for sensitivity to the antifolate pemetrexed in male and female NSCLC cell lines. Using [¹³C₆] glucose tracing in NSCLC cell lines, we found that a subset of male cells generated significantly more serine from glucose than female cells. Higher serine biosynthesis was further correlated with increased sensitivity to pemetrexed in male cells only. Concordant sex differences in metabolic gene expression were evident in NSCLC and pan-cancer transcriptome datasets, suggesting a potential mechanism with wide-reaching applicability. These data

SUBMITTER: Sponagel J 

PROVIDER: S-EPMC9619300 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature