PubMed:27084744 JSONTXT 26 Projects

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Id Subject Object Predicate Lexical cue
T1 0-128 Sentence denotes NOTCH1 and SOX10 are Essential for Proliferation and Radiation Resistance of Cancer Stem-Like Cells in Adenoid Cystic Carcinoma.
T2 129-137 Sentence denotes PURPOSE:
T3 138-351 Sentence denotes Although 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.
T4 352-469 Sentence denotes Our objective was to isolate CSC from ACC and provide insight into signaling pathways that support their propagation.
T5 470-490 Sentence denotes EXPERIMENTAL DESIGN:
T6 491-680 Sentence denotes To 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.
T7 681-689 Sentence denotes RESULTS:
T8 690-815 Sentence denotes We identified in ACC CD133-positive CSC that expressed NOTCH1 and SOX10, formed spheroids, and initiated tumors in nude mice.
T9 816-984 Sentence denotes CD133(+)ACC cells produced activated NOTCH1 (N1ICD) and generated CD133(-)cells that expressed JAG1 as well as neural differentiation factors NR2F1, NR2F2, and p27Kip1.
T10 985-1183 Sentence denotes 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.
T11 1184-1333 Sentence denotes Downstream effects ofFABP7knockdown included suppression of a broad spectrum of genes involved in proliferation, ribosome biogenesis, and metabolism.
T12 1334-1428 Sentence denotes Among proliferation-linked NOTCH1/FABP7 targets, we identified SKP2 and its substrate p27Kip1.
T13 1429-1611 Sentence denotes 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.
T14 1612-1624 Sentence denotes CONCLUSIONS:
T15 1625-1819 Sentence denotes These 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.
T16 1820-1947 Sentence denotes Sensitivity of these cells to Notch inhibition and their dependence on SKP2 offer new opportunities for targeted ACC therapies.