ArticleCell death & disease2023
Serine hydroxymethyltransferase 2 knockdown induces apoptosis in ccRCC by causing lysosomal membrane permeabilization via metabolic reprogramming.
Article in Cell death & disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 32 citations in OpenAlex.
- Pirfenidone Sensitizes Hepatic Stellate Cells to Ferroptosis by Reprogramming Glutamine and Serine Metabolism for GSH Depletion.Antioxidants (Basel, Switzerland) · 2026Article
- Glycine-GLRA1-calmodulin signaling regulates endoplasmic reticulum calcium to sustain insulin secretion and β-cell function.Life metabolism · 2026Article
- New insights into lysosomal ferroptosis-related prognostic signatures in prostate cancer: evidence from bulk and single-cell transcriptomic analysis.Frontiers in cell and developmental biology · 2026Article
- The Quartet of Core Oncogenic Drivers in Neuroendocrine Prostate Cancer: Multi-Omics Dataset Integration to Forge a Translational Link Between Biology and Precision Therapy.International journal of biological sciences · 2026Review
- The SLC1A1/EAAT3 dicarboxylic amino acid transporter is an epigenetically dysregulated nutrient carrier that sustains oncogenic metabolic programs.Nature communications · 2025Article
- Multifaceted role of serine hydroxymethyltransferase in health and disease.Molecules and cells · 2025Review
- Broadband Collision-Induced Dissociation Mass Spectrometry Imaging.Journal of the American Society for Mass Spectrometry · 2025Article
- Design, Synthesis, Anti-Tumor Activity and Molecular Docking Studies of Novel Triphenylphosphine-Containing Formononetin Derivatives.International journal of molecular sciences · 2025Article
- Lysosomes: guardians and healers within cells- multifaceted perspective and outlook from injury repair to disease treatment.Cancer cell international · 2025Review
- Efficient extraction via titanium organic frameworks facilitates in-depth profiling of urinary exosome metabolite fingerprints.Analytical and bioanalytical chemistry · 2025Article
- Mechanism and Therapeutic Progress of One-Carbon Metabolic Key Enzyme: Serine Hydroxymethyltransferase 2 in Cancer.Clinical Medicine Insights. Oncology · 2025Review
- Organoid models of ovarian cancer: resolving immune mechanisms of metabolic reprogramming and drug resistance.Frontiers in immunology · 2025Review
- Redox homeostasis of one-carbon metabolism-dependent reprogramming is critical for RCC progression under exogenous serine/glycine-deprived conditions.BMC cancer · 2024Article
- A mitochondrial-targeted activity-based sensing probe for ratiometric imaging of formaldehyde reveals key regulators of the mitochondrial one-carbon pool.Chemical science · 2024Article
- A study on the significance of serine hydroxymethyl transferase expression and its role in bladder cancer.Scientific reports · 2024Article
- Visualization of the relationship between metabolism and lung diseases from the perspective of bibliometric analysis: research trends and future prospects.Frontiers in medicine · 2024Article
- Mitophagy and clear cell renal cell carcinoma: insights from single-cell and spatial transcriptomics analysis.Frontiers in immunology · 2024Article
- Anaplastic thyroid cancer cells upregulate mitochondrial one-carbon metabolism to meet purine demand, eliciting a critical targetable vulnerability.Cancer letters · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Serine hydroxymethyltransferase 2 (SHMT2) plays an important role in converting serine to glycine and supplying carbon to one-carbon metabolism to sustain cancer cell proliferation. However, the expression, function, and underlying mechanisms of SHMT2 in clear cell renal cell carcinoma (ccRCC) remain largely unknown. In this study, we demonstrated that SHMT2 was upregulated in ccRCC tissues compared with controls and associated with patient survival. SHMT2 knockdown inhibited proliferation, migration, and invasion in ccRCC cells. Overexpression of SHMT2 promoted tumor progression. Mechanistically, SHMT2 depletion disrupted one-carbon metabolism, increased reactive oxygen species (ROS) levels, and decreased ATP levels via metabolic reprogramming, which destroyed cell homeostasis. The SHMT2 knockdown-induced stress activated autophagy. A mass of autophagosomes fused with lysosomes, resulting in lysosomal membrane permeabilization (LMP) and leakage of lysosomal contents into the cytoplasm, which eventually led to apoptosis. Our work reveals that SHMT2 functions as an oncogenic gene to promote ccRCC progression. SHMT2 depletion induces apoptosis by causing LMP through excessive activation of the autophagy-lysosome pathway via metabolic reprogramming.
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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.