Serine and Urinary Tumors

Serine is an amino acid, it comes in two forms: L-serine and D-serine. L-serine is consumed in the diet and D-serine is made in the body from L-serine. The body uses D- and L-serine to make proteins. It is a vital contributor to the folic acid cycle and serves as an important single-carbon source for tumor cells. It also supports the biosynthesis of purine and pyrimidine, participates in the methionine cycle, methylation reactions, and the generation of Nicotinamide Adenine Dinucleotide Phosphate (NADPH) for antioxidant defense and the growth and proliferation of cancer. The cells' reprogramming accelerates the breakdown of serine [1]. Serine Hydroxymethyltransferase (SHMT) 2 plays a significant role in the onset of Bladder Cancer (BLCA). The expression level of SHMT2 was found to be negatively associated with patient survivability. In vitro experiments demonstrated that bladder malignancy cells exhibited reduced motility when SHMT2 expression levels decreased. In addition, it was observed that the low levels of SHMT2 expression blocked the bladder tumor cell cycle in the G2/M phase, which led to decreased cell proliferation and increased apoptosis. SHMT2, as one of the serine hydroxymethyltransferase isozymes, is a potential cancer driver due to its influence on bladder cancer development, migration, and apoptosis.Many tumor cells show dependence on exogenous serine. Dietary serine and glycine starvation can inhibit the growth of these cancers and extend survival. In vitro, inhibition of Phosphoglycerate Dehydrogenase (PHGDH) combined with serine starvation leads to a defect in global protein synthesis, which blocks the activation of an ATF-49 (Activating Transcription Factor 4). ATF4 is a Protein Coding gene response and more broadly impacts the protective stress response to amino acid depletion. However, the defect in ATF4-response. ATF4 is a Protein Coding gene) and is seen in vitro following complete depletion of available serine. The results indicate that inhibition of PHGDH will augment the therapeutic efficacy of a serine-depleted diet [2].