دورية أكاديمية
HNF1A is a novel oncogene that regulates human pancreatic cancer stem cell properties
| العنوان: | HNF1A is a novel oncogene that regulates human pancreatic cancer stem cell properties |
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| المؤلفون: | Ethan V Abel, Masashi Goto, Brian Magnuson, Saji Abraham, Nikita Ramanathan, Emily Hotaling, Anthony A Alaniz, Chandan Kumar-Sinha, Michele L Dziubinski, Sumithra Urs, Lidong Wang, Jiaqi Shi, Meghna Waghray, Mats Ljungman, Howard C Crawford, Diane M Simeone |
| المصدر: | eLife, Vol 7 (2018) |
| بيانات النشر: | eLife Sciences Publications Ltd, 2018. |
| سنة النشر: | 2018 |
| المجموعة: | LCC:Medicine LCC:Science LCC:Biology (General) |
| مصطلحات موضوعية: | pancreatic cancer stem cells, pancreatic ductal adenocarcinoma, HNF1A, OCT4, POU5F1, patient survival, Medicine, Science, Biology (General), QH301-705.5 |
| الوصف: | The biological properties of pancreatic cancer stem cells (PCSCs) remain incompletely defined and the central regulators are unknown. By bioinformatic analysis of a human PCSC-enriched gene signature, we identified the transcription factor HNF1A as a putative central regulator of PCSC function. Levels of HNF1A and its target genes were found to be elevated in PCSCs and tumorspheres, and depletion of HNF1A resulted in growth inhibition, apoptosis, impaired tumorsphere formation, decreased PCSC marker expression, and downregulation of POU5F1/OCT4 expression. Conversely, HNF1A overexpression increased PCSC marker expression and tumorsphere formation in pancreatic cancer cells and drove pancreatic ductal adenocarcinoma (PDA) cell growth. Importantly, depletion of HNF1A in xenografts impaired tumor growth and depleted PCSC marker-positive cells in vivo. Finally, we established an HNF1A-dependent gene signature in PDA cells that significantly correlated with reduced survivability in patients. These findings identify HNF1A as a central transcriptional regulator of PCSC properties and novel oncogene in PDA. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2050-084X |
| Relation: | https://elifesciences.org/articles/33947; https://doaj.org/toc/2050-084X |
| DOI: | 10.7554/eLife.33947 |
| URL الوصول: | https://doaj.org/article/c0bbaf7b2d6f42a3bacb5bc20116432e |
| رقم الأكسشن: | edsdoj.0bbaf7b2d6f42a3bacb5bc20116432e |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 2050084X |
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| DOI: | 10.7554/eLife.33947 |