ArticlePloS one2014
ALDH1A1 maintains ovarian cancer stem cell-like properties by altered regulation of cell cycle checkpoint and DNA repair network signaling.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
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Who cites it
105 citing papers in PubMed, 169 citations in OpenAlex.
- Exploring the Utility of ALDH1 as a Marker for the Cancer Stem Cell Population in OCCC Cell Lines.Cells · 2026Article
- Aldehyde Detoxification in Cancer: Metabolic Guardians of the Genome.Biomolecules · 2026Review
- Prognostic and Predictive Significance of Cancer Stem Cell Markers (ZIP-4 and ALDH1A1) in Ovarian Serous Carcinoma Patients: An Immunohistochemical Study.Asian Pacific journal of cancer prevention : APJCP · 2026Article
- Fueling the Seed: Growth Factors and Cytokines Driving Cancer Stem Cells in Gynecological Malignancies.International journal of molecular sciences · 2025Review
- Tumoroid model recreates clinically relevant phenotypes of high grade serous ovarian cancer (HGSC) cells, carcinoma associated fibroblasts, and macrophages.Research square · 2025Article
- A comprehensive overview of ovarian cancer stem cells: correlation with high recurrence rate, underlying mechanisms, and therapeutic opportunities.Molecular cancer · 2025Review
- ALDH1A1 in breast cancer: A prospective target to overcome therapy resistance (Review).Oncology letters · 2025Review
- Circular RNAs in cancer stem cells: Insights into their roles and mechanisms (Review).International journal of molecular medicine · 2025Review
- Antisense mediated blockade of Dickkopf 1 attenuates tumor survival, metastases and bone damage in experimental osteosarcoma.Scientific reports · 2025Article
- miRNAs in radiotherapy resistance of cancer; a comprehensive review.Cell biochemistry and biophysics · 2024Review
- Exploiting Matrix Stiffness to Overcome Drug Resistance.ACS biomaterials science & engineering · 2024Review
- Metastasis-enhancing protein KITENIN confers temozolomide resistance on glioblastoma with unmethylated MGMT via upregulation of cancer stem cell makers.Clinical and translational medicine · 2024Article
- SOSTDC1 Nuclear Translocation Facilitates BTIC Maintenance and CHD1-Mediated HR Repair to Promote Tumor Progression and Olaparib Resistance in TNBC.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Informed by Cancer Stem Cells of Solid Tumors: Advances in Treatments Targeting Tumor-Promoting Factors and Pathways.International journal of molecular sciences · 2024Review
- Frizzled class receptor 5 contributes to ovarian cancer chemoresistance through aldehyde dehydrogenase 1A1.Cell communication and signaling : CCS · 2024Article
- Down-Regulation of Cysteine-Glutamate Antiporter in ALDH1A1 Expressing Oral and Breast Cancer Stem Cells Induced Oxidative Stress-Triggered Ferroptosis.Journal of Cancer · 2024Article
- Biomarkers in Cancer Detection, Diagnosis, and Prognosis.Sensors (Basel, Switzerland) · 2023Review
- Defining the Role of Metastasis-Initiating Cells in Promoting Carcinogenesis in Ovarian Cancer.Biology · 2023Review
- Downregulation of TAB182 promotes cancer stem-like cell properties and therapeutic resistance in triple-negative breast cancer cells.BMC cancer · 2023Article
- Differences and Similarities between Colorectal Cancer Cells and Colorectal Cancer Stem Cells: Molecular Insights and Implications.ACS omega · 2023Article
45 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
objectiveAldehyde dehydrogenase (ALDH) expressing cells have been characterized as possessing stem cell-like properties. We evaluated ALDH+ ovarian cancer stem cell-like properties and their role in platinum resistance.
methodsIsogenic ovarian cancer cell lines for platinum sensitivity (A2780) and platinum resistant (A2780/CP70) as well as ascites from ovarian cancer patients were analyzed for ALDH+ by flow cytometry to determine its association to platinum resistance, recurrence and survival. A stable shRNA knockdown model for ALDH1A1 was utilized to determine its effect on cancer stem cell-like properties, cell cycle checkpoints, and DNA repair mediators.
resultsALDH status directly correlated to platinum resistance in primary ovarian cancer samples obtained from ascites. Patients with ALDHHIGH displayed significantly lower progression free survival than the patients with ALDHLOW cells (9 vs. 3 months, respectively p<0.01). ALDH1A1-knockdown significantly attenuated clonogenic potential, PARP-1 protein levels, and reversed inherent platinum resistance. ALDH1A1-knockdown resulted in dramatic decrease of KLF4 and p21 protein levels thereby leading to S and G2 phase accumulation of cells. Increases in S and G2 cells demonstrated increased expression of replication stress associated Fanconi Anemia DNA repair proteins (FANCD2, FANCJ) and replication checkpoint (pS317 Chk1) were affected. ALDH1A1-knockdown induced DNA damage, evidenced by robust induction of γ-H2AX and BAX mediated apoptosis, with significant increases in BRCA1 expression, suggesting ALDH1A1-dependent regulation of cell cycle checkpoints and DNA repair networks in ovarian cancer stem-like cells.
conclusionThis data suggests that ovarian cancer cells expressing ALDH1A1 may maintain platinum resistance by altered regulation of cell cycle checkpoint and DNA repair network signaling.
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Registered trials
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.