SHMT2 (Serine Hydroxymethyltransferase 2)

Therapeutic strategies targeting metabolic vulnerabilities-including SSP blockade, cholesterol homeostasis disruption, and ferroptosis induction-show synergistic effects with conventional agents like temozolomide. This review highlights the intertwined metabolic circuits in GBM and explores their translational potential as targets for precision therapy.

In functional measurements, HDAC suppression primarily increased excitability, while SIRT suppression decreased excitability, in line with transcriptomic links. Our analysis offers insights about the role of epigenetic modifiers in regulating cardiac electrophysiology and informs the utility of hiPSC-CM as a scalable experimental model for cardiotoxicity testing of HDAC inhibitors.

Hypoxia-induced oxidized ATM maintains TNBC-CSC stemness by promoting c-Myc-dependent upregulation of MTHFD2 and SHMT2, linking hypoxia, redox signaling, and one-carbon metabolism. These findings suggest a potential therapeutic axis that could be exploited for TNBC treatment.

SHMT2 overexpression counteracted the effects of GEMIN5 knockdown, while GEMIN5 overexpression prominently reversed the regulatory effects of SHMT2 knockdown on β-catenin and GSK3β protein expression. GEMIN5-mediated m7G modification stabilizes high SHMT2 expression, which inhibits CRC cell ferroptosis and activates the Wnt/β-catenin signaling pathway in vitro.

Besides the purine metabolism, we observed that valine, leucine and isoleucine biosynthesis and degradation, TCA cycle, and propanoate metabolism were among the top pathways of DMs. In summary, we highlight the important roles of SHMT2 in HT-1376 cells and identified its downstream molecular targets, which are associated with the development of BLCA and can be used as therapeutic targets of BLCA in future.

Notably, co-inhibition of SDH and purine salvage induces pronounced antiproliferative and antitumoral effects in preclinical models. These findings reveal a signaling role for mitochondrial succinate in tuning nucleotide metabolism and highlight a dual-targeted strategy to exploit metabolic dependencies in cancer.

Ultimately, our findings underscore the importance of metabolic proteins not only as functional drivers of malignancy but also as promising candidates for biomarker discovery. Advancing their clinical implementation could significantly enhance early detection, treatment stratification, and personalized oncology.

The combination of serum metabolomics with proteomics can effectively predict the prognosis and hematologic toxicity, which can provide important data for patients to choose treatment methods.

Further studies demonstrated that compound W478 could induce cell arrest at the G2/M phase and promote cell apoptosis and ROS production in KYSE-450 and KYSE-70 cells. These findings indicated that compound W478 could serve as a promising lead compound for the development of SHMT2 inhibitor to address esophageal carcinoma.

Hypoxia initially enhanced glucose-derived methylation but later suppressed it, likely due to impaired vitamin B12-dependent remethylation of homocysteine. RQMID-MS enables precise tracking of methyl donor routing to histones and offers a robust platform for studying metabolic and epigenetic crosstalk in cancer and beyond.

Folate transporter-null HeLa cells were engineered to express RFC under the control of a tetracycline-inducible promoter...The results document the therapeutic promise of classical multitargeted pyrrolo[3,2-d]pyrimidine antifolates typified by AGF347. These novel compounds offer an exciting new platform for one-carbon-targeted drug development for cancer.

By using a mitochondrial import signal, we successfully delivered the inhibitory RNA into the mitochondria of lung cancer cells, reducing cell viability in vitro and tumor growth in vivo in a xenograft mouse model. These findings suggest that RNA-based strategies could be extended to selectively target other RNA-binding metabolic enzymes, offering potential solutions where small molecule inhibitors fall short or to counteract drug resistance.