ArticleScience advances2022
Suppression of nuclear GSK3 signaling promotes serine/one-carbon metabolism and confers metabolic vulnerability in lung cancer cells.
Article in Science advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 47 citations in OpenAlex.
- The Crosstalk Between YAP/TAZ and Cancer Metabolism: From Mechanistic Insights to Drug Discovery.International journal of molecular sciences · 2026Review
- Intraoperative drug delivery to hindbrain tumours via an injectable hydrogel is well tolerated and confers survival benefit against atypical teratoid/rhabdoid xenografts.Drug delivery and translational research · 2026Article
- MTHFR functions as a metabolic checkpoint in NSCLC through SLC25A26-mediated SHMT2 inhibition.Cell death & disease · 2026Article
- SHMT2 deficiency disrupts transcriptional regulation through homocysteine-mediated suppression of histone lactylation in Huntington's disease models.The Journal of clinical investigation · 2026Article
- Serine Hydroxymethyltransferase (SHMT) in biology and disease: molecular mechanisms and therapeutic targeting.Journal of translational medicine · 2026Review
- PSAT1 Promotes NSCLC Progression via the De Novo Serine Synthesis Pathway and Represents a Therapeutic Vulnerability.Cancer medicine · 2026Article
- Metabolic reprogramming-driven resistance to multi-kinase inhibitors in hepatocellular carcinoma: molecular mechanisms and therapeutic opportunities.Molecular cancer · 2026Review
- Integrative Bioinformatics Reveals Novel Molecular Mechanisms and Therapeutic Targets in Acute Myeloid Leukaemia.Journal of cellular and molecular medicine · 2026Article
- ZNF526 drives tumor growth by enhancing SHMT1-dependent serine metabolism and antioxidant capability in TNBC.Molecular cancer · 2025Article
- Multifaceted role of serine hydroxymethyltransferase in health and disease.Molecules and cells · 2025Review
- One-Carbon Metabolism Inhibition Depletes Purines and Results in Profound and Prolonged Ewing Sarcoma Growth Suppression.Cancer research communications · 2025Article
- Review
- SHMT inhibitor synergizes with 5-Fu to suppress gastric cancer via cell cycle arrest and chemoresistance alleviation.NPJ precision oncology · 2025Article
- Inhibition Of One-Carbon Metabolism In Ewing Sarcoma Results In Profound And Prolonged Growth Suppression Associated With Purine Depletion.bioRxiv : the preprint server for biology · 2025Article
- mTORC1, the maestro of cell metabolism and growth.Genes & development · 2025Review
- Applications and challenges of multi-omics approaches in lung cancer research and precision treatment.Frontiers in genetics · 2025Review
- Unveiling miR-1468-5p: A New Prognostic Biomarker and Therapeutic Target in Lung Adenocarcinoma.Recent patents on anti-cancer drug discovery · 2025Article
- Metabolic reprogramming and therapeutic targeting in non-small cell lung cancer: emerging insights beyond the Warburg effect.Frontiers in oncology · 2025Review
- Review
- Phosphorylated SHMT2 Regulates Oncogenesis Through mAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Serine/one-carbon metabolism provides critical resources for nucleotide biosynthesis and epigenetic maintenance and is thus necessary in cancer cell growth, although the detailed regulatory mechanisms remain unclear. We uncover a critical role of glycogen synthase kinase 3 (GSK3) in regulating the expression of serine/one-carbon metabolic enzymes. Nuclear enrichment of GSK3 significantly suppresses genes that mediate de novo serine synthesis, including PHGDH, PSAT1, PSPH, and one-carbon metabolism, including SHMT2 and MTHFD2. FRAT1 promotes nuclear exclusion of GSK3, enhances serine/one-carbon metabolism, and, as a result, confers cell vulnerability to inhibitors that target this metabolic process such as SHIN1, a specific SHMT1/2 inhibitor. Furthermore, pharmacological or genetic suppression of GSK3 promotes serine/one-carbon metabolism and exhibits a significant synergistic effect in combination with SHIN1 in suppressing cancer cell proliferation in cultured cells and in vivo. Our observations indicate that inhibition of nuclear GSK3 signaling creates a vulnerability, which results in enhanced efficacy of serine/one-carbon metabolism inhibitors for the treatment of cancer.
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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.