ArticleOncotarget2016
5-FU targets rpL3 to induce mitochondrial apoptosis via cystathionine-β-synthase in colon cancer cells lacking p53.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 78 citations in OpenAlex.
- Beyond the Ribosome: The Expanding Role of the Nucleolus in Neurodegenerative Pathways.Molecular neurobiology · 2026Review
- The Nucleolus in Human Disease: Ribosome Biogenesis, Nucleolar Surveillance, and Therapeutic Opportunities.Biomolecules · 2026Review
- Preferential Upregulation of AMOT-p80 Is Associated with YAP-Linked Resistance to 5-Fluorouracil and Oxaliplatin in Colorectal Cancer Cells.Biomolecules · 2026Article
- Reversing uL3-mediated chemoresistance through synergistic combination of 5-FU and G-quadruplex ligands.NAR cancer · 2025Article
- Extra-Ribosomal Roles for Ribosomal Proteins and Their Relevance to Tumour Suppression, Carcinogenesis and Cancer Progression.Cancers · 2025Review
- The synergistic antitumour effect of Carrimycin combined with 5-fluorouracil on colorectal cancer.Scientific reports · 2025Article
- Cystathionine-The Journal of international medical research · 2024Article
- The potential role of hydrogen sulfide in cancer cell apoptosis.Cell death discovery · 2024Review
- Role of Hydrogen Sulfide in Oncological and Non-Oncological Disorders and Its Regulation by Non-Coding RNAs: A Comprehensive Review.Non-coding RNA · 2024Review
- The Effects of Deregulated Ribosomal Biogenesis in Cancer.Biomolecules · 2023Review
- Dynamic interplay between RPL3- and RPL3L-containing ribosomes modulates mitochondrial activity in the mammalian heart.Nucleic acids research · 2023Article
- Ferroptosis: From regulation of lipid peroxidation to the treatment of diseases.Cell biology and toxicology · 2023Review
- Combining β-Carotene with 5-FU via Polymeric Nanoparticles as a Novel Therapeutic Strategy to Overcome uL3-Mediated Chemoresistance in p53-Deleted Colorectal Cancer Cells.Molecular pharmaceutics · 2023Article
- Nucleolar stress: Molecular mechanisms and related human diseases.Cancer science · 2023Review
- Combination of Copper Metallodendrimers with Conventional Antitumor Drugs to Combat Cancer in In Vitro Models.International journal of molecular sciences · 2023Article
- Antioxidant and anti-inflammatory activities of lycopene against 5-fluorouracil-induced cytotoxicity in Caco2 cells.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2022Article
- Article
- Emerging roles of cystathionine β-synthase in various forms of cancer.Redox biology · 2022Review
- Proteomic profiling of cisplatin-resistant and cisplatin-sensitive germ cell tumour cell lines using quantitative mass spectrometry.World journal of urology · 2022Article
- 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
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent findings revealed in cancer cells novel stress response pathways, which in response to many chemotherapeutic drugs causing nucleolar stress, will function independently from tumor protein p53 (p53) and still lead to cell cycle arrest and/or apoptosis. Since it is known that most cancers lack functional p53, it is of great interest to explore these emerging molecular mechanisms. Here, we demonstrate that nucleolar stress induced by 5-fluorouracil (5-FU) in colon cancer cells devoid of p53 leads to the activation of ribosomal protein L3 (rpL3) as proapoptotic factor. rpL3, as ribosome-free form, is a negative regulator of cystathionine-β-synthase (CBS) expression at transcriptional level through a molecular mechanism involving Sp1. The rpL3-CBS association affects CBS stability and, in addition, can trigger CBS translocation into mitochondria. Consequently apoptosis will be induced through the mitochondrial apoptotic cell death pathway characterized by an increased ratio of Bax to Bcl-2, cytochrome c release and subsequent caspase activation. It is noteworthy that silencing of CBS is associated to a strong increase of 5-FU-mediated inhibition of cell migration and proliferation. These data reveal a novel mechanism to accomplish p53-independent apoptosis and suggest a potential therapeutic approach aimed at upregulating rpL3 for treating cancers lacking p53.
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