SHMT1 (Serine Hydroxymethyltransferase 1)

Finally, studies in Drosophila have shown that PLP deficiency can promote tumor development by also triggering the loss of heterozygosity (LOH). These findings highlight Drosophila as a powerful tool to elucidate the molecular pathways linking vitamin B6 deficiency to cancer.

SHMT depletion in RasV12DlgRNAi cells causes DNA and chromosome damage and renders these cells sensitive to genotoxic stressors such as X-rays or hydroxyurea...Taken together, our data suggest that a diminished SHMT activity may drive the progression of RasV12DlgRNAi cancers through ROS-induced genome instability. Additionally, our study points to a novel gene-nutrient interaction, SHMT-PLP, that impacts cancer growth with potential therapeutic implications.

By integrating germline (GWAS-based) and somatic evidence, this study provides a comprehensive view of HCC pathogenesis. This integrated strategy successfully identified a core set of genes and proteins with potential causal links to HCC, elucidating their functional convergence in cancer biology. These findings offer novel molecular insights and candidate targets for precise diagnosis, prognostic assessment, and targeted therapy of HCC, laying a solid foundation for future translational research.

We conclude that reduced thymidylate synthesis causes folic acid-responsive NTDs and PN in mice and that diabetes sensitizes mice to folic acid-responsive PN. Diabetes induces a special nutritional requirement for high intake of folic acid to prevent PN.

Biomarkers such as xCT/GPX4 expression, PHGDH levels, Nrf2 activity, and GSH/NADPH ratios may guide patient stratification and response prediction. Overall, understanding the redox-amino acid metabolic network provides a mechanistic basis and translational opportunities for precision metabolic therapies in ovarian cancer.

Analysis of γH2AX demonstrates a prolonged duration of foci formation in cells after proton irradiation in the presence of BSH11. Further research will be needed to better understand the potential clinical applications of proton-boron interaction.

This study presents a validated prognostic risk score model comprising AAMRGs in LSCC. Furthermore, our findings highlight the downregulation of SHMT1 in LSCC and its significant association with patient prognosis and tumor stage.

Considering expression frequency, specificity, and functional relevance, FTCD, GPD1, SOD2, and EIF4B Ser422 phosphorylation are further identified and validated as subtype prognostic biomarkers. This study provides critical insights into the molecular mechanisms underlying CRLM and offers resources for high-risk metastatic CRC.

Our results revealed significant associations between amino acid metabolism gene polymorphisms and PTC risk, suggesting potential biomarkers for PTC susceptibility.

Furthermore, we obtained an X-ray structure of TthSHMT in complex with the substrate THF, which binds identically as 5MTHF at the peripheral binding site. The unique structural and functional information provided by neutron crystallography, in combination with X-ray structures, can be employed in the rational design of SHMT inhibitors.

While current evidence is predominantly preclinical, sertraline's multi-targeted action and established safety profile support its candidacy for repurposing. Further translational research and biomarker-driven clinical trials are warranted to validate its therapeutic niche and optimize its integration into oncology.