ArticlePloS one2012
Frequent epigenetic silencing of the folate-metabolising gene cystathionine-beta-synthase in gastrointestinal cancer.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 62 citations in OpenAlex.
- The Mechanism and Regulation of Disulfidptosis and Its Role in Disease.Biomedicines · 2026Review
- Retraction: Progesterone potentiates the growth inhibitory effects of calcitriol in endometrial cancer via suppression of CYP24A1.Oncotarget · 2026Article
- Explore the role of CBS in stomach adenocarcinoma based on the sulfur-containing amino acid metabolism network.Scientific reports · 2025Article
- Amino acids in cancer: Understanding metabolic plasticity and divergence for better therapeutic approaches.Cell reports · 2025Review
- The nonessential amino acid cysteine is required to prevent ferroptosis in acute myeloid leukemia.Blood advances · 2024Article
- Metabolic profiling stratifies colorectal cancer and reveals adenosylhomocysteinase as a therapeutic target.Nature metabolism · 2023Article
- Targeting Homocysteine and Hydrogen Sulfide Balance as Future Therapeutics in Cancer Treatment.Antioxidants (Basel, Switzerland) · 2023Review
- Mechanism of Cell Death by Combined Treatment with an xCT Inhibitor and Paclitaxel: An Alternative Therapeutic Strategy for Patients with Ovarian Clear Cell Carcinoma.International journal of molecular sciences · 2023Article
- Discovery of decreased ferroptosis in male colorectal cancer patients with KRAS mutations.Redox biology · 2023Article
- Discovery of decreased ferroptosis in male colorectal cancer patients with KRAS mutations.bioRxiv : the preprint server for biology · 2023Article
- Cystathionine β-synthase affects organization of cytoskeleton and modulates carcinogenesis in colorectal carcinoma cells.Frontiers in oncology · 2023Article
- Transsulfuration, minor player or crucial for cysteine homeostasis in cancer.Trends in cell biology · 2022Review
- Article
- Hydrogen Sulfide Biology and Its Role in Cancer.Molecules (Basel, Switzerland) · 2022Review
- Hypoxia inducible lncRNA-CBSLR modulates ferroptosis through m6A-YTHDF2-dependent modulation of CBS in gastric cancer.Journal of advanced research · 2022Article
- Induction and application of ferroptosis in cancer therapy.Cancer cell international · 2022Review
- Cystathionine β-synthase expression correlates with tumor development and poor prognosis in patients with adenocarcinoma of the gastroesophageal junction.American journal of translational research · 2022Article
- Impact of the glutathione synthesis pathway on sulfasalazine-treated endometrial cancer.Oncotarget · 2022Article
- The Hidden Role of Hydrogen Sulfide Metabolism in Cancer.International journal of molecular sciences · 2021Review
- Highly recurrent CBS epimutations in gastric cancer CpG island methylator phenotypes and inflammation.Genome biology · 2021Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBoth gastric and colorectal cancers (CRC) are the most frequently occurring malignancies worldwide with the overall survival of these patients remains unsatisfied. Identification of tumor suppressor genes (TSG) silenced by promoter CpG methylation uncovers mechanisms of tumorigenesis and identifies new epigenetic biomarkers for early cancer detection and prognosis assessment. Cystathionine-beta-synthase (CBS) functions in the folate metabolism pathway, which is intricately linked to methylation of genomic DNA. Dysregulation of DNA methylation contributes substantially to cancer development. METHODOLOGY/PRINCIPAL
findingsTo identify potential TSGs silenced by aberrant promoter methylation in CRC, we analyzed tumor and adjacent tissues from CRC cases using the Illumina Human Methylation45 BeadChip. We identified hypermethylation of the CBS gene in CRC samples, compared to adjacent tissues. Methylation and decreased mRNA expression of CBS were detected in most CRC cell lines by methylation-specific PCR and semiquantitative RT-PCR, as well as in gastric cancer. Treatment with 5-aza-2'-deoxycytidine and/or trichostatin A reversed methylation and restored CBS mRNA expression indicating a direct effect. Aberrant methylation was further detected in 31% of primary CRCs (29 of 96) and 55% of gastric tumors (11 of 20). In contrast, methylation was seldom found in normal tissues adjacent to the tumor. CBS methylation was associated with KRAS mutations in primary CRCs (P = 0.04, by χ(2)-test). However, no association was found between CBS methylation or KRAS mutations with cancer relapse/metastasis in Stage II CRC patients.
conclusionA novel finding from this study is that the folate metabolism enzyme CBS mRNA levels are frequently downregulated through CpG methylation of the CBS gene in gastric cancer and CRC, suggesting that CBS functions as a tumor suppressor gene. These findings warrant further study of CBS as an epigenetic biomarker for molecular diagnosis of gastrointestinal cancers.
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