ArticleMolecular cancer therapeutics2012
A systems biology approach identifies SART1 as a novel determinant of both 5-fluorouracil and SN38 drug resistance in colorectal cancer.
Article in Molecular cancer therapeutics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 41 citations in OpenAlex.
- Partial Depletion of SART1 Selectively Induces Mitotic Defects and Cell Death in Cancer Cells.Genes to cells : devoted to molecular & cellular mechanisms · 2026Article
- Cavin gene family and caveolae-related disorders: pathogenetic roles and possible mechanisms.Cell communication and signaling : CCS · 2026Review
- Secretory exosomes from modified immune cells against cancer.Medical oncology (Northwood, London, England) · 2025Review
- Potential role of CFLAR in enhancing 5-FU sensitivity and modulating immune cell infiltration in breast cancer.European journal of medical research · 2025Article
- Comprehensive analysis of the prognostic and immunological role of cavins in non-small cell lung cancer.BMC cancer · 2024Article
- SART1 modulates poly-(ADP-ribose) chain accumulation and PARP1 chromatin localization.iScience · 2024Article
- Involvement of the splicing factor SART1 in the BRCA1-dependent homologous recombination repair of DNA double-strand breaks.Scientific reports · 2024Article
- MDF is a conserved splicing factor and modulates cell division and stress response inLife science alliance · 2023Article
- Cell-cycle and apoptosis related and proteomics-based signaling pathways of human hepatoma Huh-7 cells treated by three currently used multi-RTK inhibitors.Frontiers in pharmacology · 2022Article
- Predicting Agents That Can Overcome 5-FU Resistance in Colorectal Cancers via Pharmacogenomic Analysis.Biomedicines · 2021Article
- ACells · 2020Article
- MicroRNA-375-3p enhances chemosensitivity to 5-fluorouracil by targeting thymidylate synthase in colorectal cancer.Cancer science · 2020Article
- Plasma and Tissue Specific miRNA Expression Pattern and Functional Analysis Associated to Colorectal Cancer Patients.Cancers · 2020Article
- Correlation of the invasive potential of glioblastoma and expression of caveola-forming proteins caveolin-1 and CAVIN1.Journal of neuro-oncology · 2019Article
- Regulation of proliferation and cell cycle by protein regulator of cytokinesis 1 in oral squamous cell carcinoma.Cell death & disease · 2018Article
- PTRF suppresses the progression of colorectal cancers.Oncotarget · 2017Article
- New frontiers in the treatment of colorectal cancer: Autophagy and the unfolded protein response as promising targets.Autophagy · 2017Review
- Network-based expression analysis reveals key genes related to glucocorticoid resistance in infant acute lymphoblastic leukemia.Cellular oncology (Dordrecht, Netherlands) · 2017Article
- Fibroblast growth factor receptor 4 (FGFR4): a targetable regulator of drug resistance in colorectal cancer.Cell death & disease · 2014Article
- Caveola-forming proteins caveolin-1 and PTRF in prostate cancer.Nature reviews. Urology · 2013Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Chemotherapy response rates for advanced colorectal cancer remain disappointingly low, primarily because of drug resistance, so there is an urgent need to improve current treatment strategies. To identify novel determinants of resistance to the clinically relevant drugs 5-fluorouracil (5-FU) and SN38 (the active metabolite of irinotecan), transcriptional profiling experiments were carried out on pretreatment metastatic colorectal cancer biopsies and HCT116 parental and chemotherapy-resistant cell line models using a disease-specific DNA microarray. To enrich for potential chemoresistance-determining genes, an unsupervised bioinformatics approach was used, and 50 genes were selected and then functionally assessed using custom-designed short interfering RNA (siRNA) screens. In the primary siRNA screen, silencing of 21 genes sensitized HCT116 cells to either 5-FU or SN38 treatment. Three genes (RAPGEF2, PTRF, and SART1) were selected for further analysis in a panel of 5 colorectal cancer cell lines. Silencing SART1 sensitized all 5 cell lines to 5-FU treatment and 4/5 cell lines to SN38 treatment. However, silencing of RAPGEF2 or PTRF had no significant effect on 5-FU or SN38 sensitivity in the wider cell line panel. Further functional analysis of SART1 showed that its silencing induced apoptosis that was caspase-8 dependent. Furthermore, silencing of SART1 led to a downregulation of the caspase-8 inhibitor, c-FLIP, which we have previously shown is a key determinant of drug resistance in colorectal cancer. This study shows the power of systems biology approaches for identifying novel genes that regulate drug resistance and identifies SART1 as a previously unidentified regulator of c-FLIP and drug-induced activation of caspase-8.
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