ArticleOncogene2021
The loss of SHMT2 mediates 5-fluorouracil chemoresistance in colorectal cancer by upregulating autophagy.
Article in Oncogene, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 58 citations in OpenAlex.
- A Novel Loss-of-Function Variant inGenes · 2026Article
- Mitochondrial metabolism determines chemotherapy sensitivity in colorectal cancer.Nature metabolism · 2026Article
- Article
- Serine Hydroxymethyltransferase (SHMT) in biology and disease: molecular mechanisms and therapeutic targeting.Journal of translational medicine · 2026Review
- Cell Line-Dependent Cell Death Pathways Induced by Thymoquinone in Colorectal Cancer Cells.Molecules (Basel, Switzerland) · 2026Article
- Electrolyzed Hydrogen Water Improves Chemosensitivity to Anticancer Drugs by Potently Suppressing Autophagy.Journal of cellular and molecular medicine · 2026Article
- Research on serine hydroxymethyltransferase 2 mechanisms in malignant tumor development and progression.PeerJ · 2026Review
- One-carbon metabolism in cancer: moonlighting functions of metabolic enzymes and anti-tumor therapy.Cancer metastasis reviews · 2025Review
- Serum multiomics prediction of prognosis and adverse reactions to concurrent chemoradiotherapy in patients with esophageal cancer.British journal of cancer · 2025Article
- FOXS1, frequently inactivated by promoter methylation, inhibited colorectal cancer cell growth by promoting TGFBI degradation through autophagy-lysosome pathway.Journal of advanced research · 2025Article
- Multifaceted role of serine hydroxymethyltransferase in health and disease.Molecules and cells · 2025Review
- Guanine monophosphate synthase-mediated nuclear and mitochondrial communication in the progression of gastric cancer.Translational cancer research · 2025Article
- CRISPR/Cas9 system: a novel approach to overcome chemotherapy and radiotherapy resistance in cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- CLDN6 induces chemoresistance through protective autophagy in breast cancer.International journal of biological sciences · 2025Article
- Suppressing GDF15 enhances the chemotherapeutic effect of 5 FU on MSI-H CRC by regulating the ferroptosis pathway SLC7A11/GSH/GPX4.Journal of cancer research and clinical oncology · 2024Article
- Hypoxia-induced SHMT2 protein lactylation facilitates glycolysis and stemness of esophageal cancer cells.Molecular and cellular biochemistry · 2024Article
- TM9SF1 expression correlates with autoimmune disease activity and regulates antibody production through mTOR-dependent autophagy.BMC medicine · 2024Article
- Connecting dots between nucleotide biosynthesis and DNA lesion repair/bypass in cancer.Bioscience reports · 2024Review
- Construction and validation of a folate metabolism-related gene signature for predicting prognosis in HNSCC.Journal of cancer research and clinical oncology · 2024Article
- SHMT2 promotes papillary thyroid cancer metastasis through epigenetic activation of AKT signaling.Cell death & disease · 2024Article
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
5-Fluorouracil (5-FU)-based chemotherapy is the first-line treatment for colorectal cancer (CRC) but is hampered by chemoresistance. Despite its impact on patient survival, the mechanism underlying chemoresistance against 5-FU remains poorly understood. Here, we identified serine hydroxymethyltransferase-2 (SHMT2) as a critical regulator of 5-FU chemoresistance in CRC. SHMT2 inhibits autophagy by binding cytosolic p53 instead of metabolism. SHMT2 prevents cytosolic p53 degradation by inhibiting the binding of p53 and HDM2. Under 5-FU treatment, SHMT2 depletion promotes autophagy and inhibits apoptosis. Autophagy inhibitors decrease low SHMT2-induced 5-FU resistance in vitro and in vivo. Finally, the lethality of 5-FU treatment to CRC cells was enhanced by treatment with the autophagy inhibitor chloroquine in patient-derived and CRC cell xenograft models. Taken together, our findings indicate that autophagy induced by low SHMT2 levels mediates 5-FU resistance in CRC. These results reveal the SHMT2-p53 interaction as a novel therapeutic target and provide a potential opportunity to reduce chemoresistance.
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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.