ArticleMolecular biology of the cell2009
Reduced ATR or Chk1 expression leads to chromosome instability and chemosensitization of mismatch repair-deficient colorectal cancer cells.
Article in Molecular biology of the cell, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 40 citations in OpenAlex.
- Early mutational events and clonal dynamics in normal crypts: implications for colorectal tumorigenesis.Human genomics · 2025Review
- REV3 promotes cellular tolerance to 5-fluorodeoxyuridine by activating translesion DNA synthesis and intra-S checkpoint.PLoS genetics · 2024Article
- Mutational separation and clinical outcomes ofWorld journal of gastrointestinal surgery · 2023Article
- ATF2 loss promotes 5-FU resistance in colon cancer cells via activation of the ATR-Chk1 damage response pathway.BMC cancer · 2023Article
- Immunosuppressive Signaling Pathways as Targeted Cancer Therapies.Biomedicines · 2022Review
- MLH1 Deficiency-Triggered DNA Hyperexcision by Exonuclease 1 Activates the cGAS-STING Pathway.Cancer cell · 2021Article
- FLT3-ITD cooperates with Rac1 to modulate the sensitivity of leukemic cells to chemotherapeutic agents via regulation of DNA repair pathways.Haematologica · 2019Article
- DNA Damage Response-Independent Role for MDC1 in Maintaining Genomic Stability.Molecular and cellular biology · 2017Article
- Zbtb1 Safeguards Genome Integrity and Prevents p53-Mediated Apoptosis in Proliferating Lymphoid Progenitors.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- Cdc6 contributes to cisplatin-resistance by activation of ATR-Chk1 pathway in bladder cancer cells.Oncotarget · 2016Article
- Distinct gene expression signatures in lynch syndrome and familial colorectal cancer type x.PloS one · 2013Article
- Identification of DNA repair pathways that affect the survival of ovarian cancer cells treated with a poly(ADP-ribose) polymerase inhibitor in a novel drug combination.Molecular pharmacology · 2012Article
- Selective tumor killing based on specific DNA-damage response deficiencies.Cancer biology & therapy · 2012Review
- P38MAPK is a major determinant of the balance between apoptosis and autophagy triggered by 5-fluorouracil: implication in resistance.Oncogene · 2012Article
- Analysis of mutations that dissociate G(2) and essential S phase functions of human ataxia telangiectasia-mutated and Rad3-related (ATR) protein kinase.The Journal of biological chemistry · 2011Article
- Poly(ADP-Ribose) polymerase inhibition synergizes with 5-fluorodeoxyuridine but not 5-fluorouracil in ovarian cancer cells.Cancer research · 2011Article
- Glucose deprivation is associated with Chk1 degradation through the ubiquitin-proteasome pathway and effective checkpoint response to replication blocks.Biochimica et biophysica acta · 2011Article
- Article
- Prospects for the Use of ATR Inhibitors to Treat Cancer.Pharmaceuticals (Basel, Switzerland) · 2010Review
- Trial Watch: Targeting ATM-CHK2 and ATR-CHK1 pathways for anticancer therapy.Molecular & cellular oncologyReview
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Genomic instability in colorectal cancer is categorized into two distinct classes: chromosome instability (CIN) and microsatellite instability (MSI). MSI is the result of mutations in the mismatch repair (MMR) machinery, whereas CIN is often thought to be associated with a disruption in the APC gene. Clinical data has recently shown the presence of heterozygous mutations in ATR and Chk1 in human cancers that exhibit MSI, suggesting that those mutations may contribute to tumorigenesis. To determine whether reduced activity in the DNA damage checkpoint pathway would cooperate with MMR deficiency to induce CIN, we used siRNA strategies to partially decrease the expression of ATR or Chk1 in MMR-deficient colorectal cancer cells. The resultant cancer cells display a typical CIN phenotype, as characterized by an increase in the number of chromosomal abnormalities. Importantly, restoration of MMR proficiency completely inhibited induction of the CIN phenotype, indicating that the combination of partial checkpoint blockage and MMR deficiency is necessary to trigger CIN. Moreover, disruption of ATR and Chk1 in MMR-deficient cells enhanced the sensitivity to treatment with the commonly used colorectal chemotherapeutic compound, 5-fluorouracil. These results provide a basis for the development of a combination therapy for those cancer patients.
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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.