ArticleClinical cancer research : an official journal of the American Association for Cancer Research2016
NOTCH1 and SOX10 are Essential for Proliferation and Radiation Resistance of Cancer Stem-Like Cells in Adenoid Cystic Carcinoma.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- Deciphering NOTCH1 as a Biomarker in Adenoid Cystic Carcinoma: Insights From a Systematic Review With Meta-Analysis.Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology · 2025Pooled it
- AKT, ATR, and Notch Inhibitors Radiosensitize a Preclinical Model of Adenoid Cystic Carcinoma.Head & neck · 2026Article
- The SOX gene superfamily in oncogenesis: unraveling links to ncRNAs, key pathways, chemoresistance, and gene editing approaches.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Review
- Notch signaling pathway in cancer: from mechanistic insights to targeted therapies.Signal transduction and targeted therapy · 2024Review
- Review
- Inverse agonists of retinoic acid receptor/retinoid X receptor signaling as lineage-specific antitumor agents against human adenoid cystic carcinoma.Journal of the National Cancer Institute · 2023Article
- Knockdown of circ_0005615 enhances the radiosensitivity of colorectal cancer by regulating the miR-665/NOTCH1 axis.Open medicine (Warsaw, Poland) · 2023Article
- AL101, a gamma-secretase inhibitor, has potent antitumor activity against adenoid cystic carcinoma with activated NOTCH signaling.Cell death & disease · 2022Article
- The Immunohistochemical Expression of SOX-10 in Urothelial Carcinoma and the Non Neoplastic Urothelium; and a Correlation with the Tumor Features.Asian Pacific journal of cancer prevention : APJCP · 2022Article
- Review
- The interaction of SKP2 with p27 enhances the progression and stemness of osteosarcoma.Annals of the New York Academy of Sciences · 2021Article
- Targeting cancer stem cells for reversing therapy resistance: mechanism, signaling, and prospective agents.Signal transduction and targeted therapy · 2021Review
- Unlocking the Secrets of Cancer Stem Cells with γ-Secretase Inhibitors: A Novel Anticancer Strategy.Molecules (Basel, Switzerland) · 2021Review
- Conditional Cell Reprogramming in Modeling Digestive System Diseases.Frontiers in cell and developmental biology · 2021Review
- Cancer stem cells in head and neck cancer.American journal of stem cells · 2021Review
- Systemic therapies for salivary gland adenoid cystic carcinoma.American journal of cancer research · 2021Review
- Molecular and Cellular Modelling of Salivary Gland Tumors Open New Landscapes in Diagnosis and Treatment.Cancers · 2020Review
- Conditional reprogramming: next generation cell culture.Acta pharmaceutica Sinica. B · 2020Review
- Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
purposeAlthough the existence of cancer stem cells (CSC) in adenoid cystic carcinoma (ACC) has been proposed, lack of assays for their propagation and uncertainty about molecular markers prevented their characterization. Our objective was to isolate CSC from ACC and provide insight into signaling pathways that support their propagation. EXPERIMENTAL
designTo isolate CSC from ACC and characterize them, we used ROCK inhibitor-supplemented cell culture, immunomagnetic cell sorting, andin vitro/in vivoassays for CSC viability and tumorigenicity.
resultsWe identified in ACC CD133-positive CSC that expressed NOTCH1 and SOX10, formed spheroids, and initiated tumors in nude mice. CD133(+)ACC cells produced activated NOTCH1 (N1ICD) and generated CD133(-)cells that expressed JAG1 as well as neural differentiation factors NR2F1, NR2F2, and p27Kip1. Knockdowns ofNOTCH1, SOX10, and their common effectorFABP7had negative effects on each other, inhibited spheroidogenesis, and induced cell death pointing at their essential roles in CSC maintenance. Downstream effects ofFABP7knockdown included suppression of a broad spectrum of genes involved in proliferation, ribosome biogenesis, and metabolism. Among proliferation-linked NOTCH1/FABP7 targets, we identified SKP2 and its substrate p27Kip1. A γ-secretase inhibitor, DAPT, selectively depleted CD133(+)cells, suppressed N1ICD and SKP2, induced p27Kip1, inhibited ACC growthin vivo, and sensitized CD133(+)cells to radiation.
conclusionsThese results establish in the majority of ACC the presence of a previously uncharacterized population of CD133(+)cells with neural stem properties, which are driven by SOX10, NOTCH1, and FABP7. Sensitivity of these cells to Notch inhibition and their dependence on SKP2 offer new opportunities for targeted ACC therapies.
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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.