ArticleInternational journal of molecular sciences2019
Nanog Signaling Mediates Radioresistance in ALDH-Positive Breast Cancer Cells.
Article in International journal of molecular sciences, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Molecular Biomarkers of Radiosensitivity and Radioresistance in Cervical Cancer: A Systematic Review.International journal of molecular sciences · 2026Pooled it
- Tumor heterogeneity: development, mechanisms, and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- The metabolic profiles of cancer stem cells.Stem cell research & therapy · 2026Review
- Prognostic Value of SOX2 and NANOG Expression in Recurrent Oral Squamous Cell Carcinoma.Cancers · 2025Article
- The Significance of Aldehyde Dehydrogenase 1 in Cancers.International journal of molecular sciences · 2024Review
- Targeting cancer stem cells by TPA leads to inhibition of refractory sarcoma and extended overall survival.Molecular therapy. Oncology · 2024Article
- Targeted therapy of cancer stem cells: inhibition of mTOR in pre-clinical and clinical research.Cell death & disease · 2024Review
- Transcriptional regulation of cancer stem cell: regulatory factors elucidation and cancer treatment strategies.Journal of experimental & clinical cancer research : CR · 2024Review
- ALDEFLUOR activity, ALDH isoforms, and their clinical significance in cancers.Journal of enzyme inhibition and medicinal chemistry · 2023Article
- The strategies to cure cancer patients by eradicating cancer stem-like cells.Molecular cancer · 2023Review
- Multi-omics profiling reveals cellular pathways and functions regulated by ALDH1B1 in colon cancer cells.Chemico-biological interactions · 2023Article
- Human Aldehyde Dehydrogenases: A Superfamily of Similar Yet Different Proteins Highly Related to Cancer.Cancers · 2023Review
- Article
- Targeting Breast Cancer Stem Cells.International journal of biological sciences · 2023Review
- Review
- ALDH1: A potential therapeutic target for cancer stem cells in solid tumors.Frontiers in oncology · 2022Review
- 3D Breast Tumor Models for Radiobiology Applications.Cancers · 2021Review
- Knockdown of the prognostic cancer stem cell marker Musashi-1 decreases radio-resistance while enhancing apoptosis in hormone receptor-positive breast cancer cells via p21Journal of cancer research and clinical oncology · 2021Article
- Nanog, in Cooperation with AP1, Increases the Expression of E6/E7 Oncogenes from HPV Types 16/18.Viruses · 2021Article
- RBM5-AS1 promotes radioresistance in medulloblastoma through stabilization of SIRT6 protein.Acta neuropathologica communications · 2021Article
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
Recently, cancer stem cells (CSCs) have been identified as the major cause of both chemotherapy and radiotherapy resistance. Evidence from experimental studies applying both in vitro and in vivo preclinical models suggests that CSCs survive after conventional therapy protocols. Several mechanisms are proposed to be involved in CSC resistance to radiotherapy. Among them, stimulated DNA double-strand break (DSB) repair capacity in association with aldehyde dehydrogenase (ALDH) activity seems to be the most prominent mechanism. However, thus far, the pathway through which ALDH activity stimulates DSB repair is not known. Therefore, in the present study, we investigated the underlying signaling pathway by which ALDH activity stimulates DSB repair and can lead to radioresistance of breast cancer cell lines in vitro. When compared with ALDH-negative cells, ALDH-positive cells presented significantly enhanced cell survival after radiation exposure. This enhanced cell survival was associated with stimulated Nanog, BMI1 and Notch1 protein expression, as well as stimulated Akt activity. By applying overexpression and knockdown approaches, we clearly demonstrated that Nanog expression is associated with enhanced ALDH activity and cellular radioresistance, as well as stimulated DSB repair. Akt and Notch1 targeting abrogated the Nanog-mediated radioresistance and stimulated ALDH activity. Overall, we demonstrate that Nanog signaling induces tumor cell radioresistance and stimulates ALDH activity, most likely through activation of the Notch1 and Akt pathways.
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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.