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. |