ArticleCell death & disease2024
SHMT2 promotes papillary thyroid cancer metastasis through epigenetic activation of AKT signaling.
Article in Cell death & disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 21 citations in OpenAlex.
- Epitranscriptomic Regulation of ALDOA by SHMT2-Mediated m6A Modification Drives Gastric Cancer Malignancy.Molecular carcinogenesis · 2026Article
- Role of methionine metabolism in cancer: recent advances in molecular mechanisms and therapeutic implications.Experimental hematology & oncology · 2026Review
- MTHFR functions as a metabolic checkpoint in NSCLC through SLC25A26-mediated SHMT2 inhibition.Cell death & disease · 2026Article
- Tumor suppressor function of SHMT in a Drosophila RasCell death & disease · 2026Article
- The molecular mechanisms and potential therapeutic implications of the crosstalk between DNA methylation and metabolic reprogramming in thyroid cancer.Cell death discovery · 2026Review
- Targeting one-carbon metabolic vulnerabilities of metastasis with therapeutic potential.bioRxiv : the preprint server for biology · 2026Article
- Targetable pathways for drug repurposing in gastric cancer.World journal of gastroenterology · 2025Review
- Exosome-mediated metabolic reprogramming: effects on thyroid cancer progression and tumor microenvironment remodeling.Molecular cancer · 2025Review
- Epigenetic control in thyroid cancer: mechanisms and clinical perspective.Cell death discovery · 2025Review
- SHMT2 overexpression improves glaucoma by enhancing mitophagy in retinal ganglion cells through promoting the phospho of PINK1.Diagnostic pathology · 2025Article
- Design, Synthesis, Anti-Tumor Activity and Molecular Docking Studies of Novel Triphenylphosphine-Containing Formononetin Derivatives.International journal of molecular sciences · 2025Article
- Serine Hydroxymethyltransferase Modulates Midgut Physiology inBiomolecules · 2025Article
- Systems biology approach delineates critical pathways associated with papillary thyroid cancer: a multi-omics data analysis.Thyroid research · 2025Article
- Bridging epigenomics and tumor immunometabolism: molecular mechanisms and therapeutic implications.Molecular cancer · 2025Review
- Mechanism and Therapeutic Progress of One-Carbon Metabolic Key Enzyme: Serine Hydroxymethyltransferase 2 in Cancer.Clinical Medicine Insights. Oncology · 2025Review
- TM4SF4 is a diagnostic biomarker accelerating progression of papillary thyroid cancer via AKT pathway.Cancer biology & therapy · 2024Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Cancer cells alter their metabolism and epigenetics to support cancer progression. However, very few modulators connecting metabolism and epigenetics have been uncovered. Here, we reveal that serine hydroxymethyltransferase-2 (SHMT2) generates S-adenosylmethionine (SAM) to epigenetically repress phosphatase and tensin homolog (PTEN), leading to papillary thyroid cancer (PTC) metastasis depending on activation of AKT signaling. SHMT2 is elevated in PTC, and is associated with poor prognosis. Overexpressed SHMT2 promotes PTC metastasis both in vitro and in vivo. Proteomic enrichment analysis shows that AKT signaling is activated, and is positively associated with SHMT2 in PTC specimens. Blocking AKT activation eliminates the effects of SHMT2 on promoting PTC metastasis. Furthermore, SHMT2 expression is negatively associated with PTEN, a negative AKT regulator, in PTC specimens. Mechanistically, SHMT2 catalyzes serine metabolism and produces activated one-carbon units that can generate SAM for the methylation of CpG islands in PTEN promoter for PTEN suppression and following AKT activation. Importantly, interference with PTEN expression affects SHMT2 function by promoting AKT signaling activation and PTC metastasis. Collectively, our research demonstrates that SHMT2 connects metabolic reprogramming and epigenetics, contributing to the poor progression of PTC.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.