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| Status |
Public on Nov 27, 2017 |
| Title |
PDX1 dynamically regulates pancreatic ductal adenocarcinoma initiation and maintenance [RNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Aberrant activation of embryonic signaling pathways is frequent in pancreatic ductal adenocarcinoma (PDA) making developmental regulators therapeutically attractive. Here, we demonstrate diverse functions for PDX1, a transcription factor indispensable for pancreas development, in the progression from normal exocrine cells to metastatic PDA. We identify a critical role for PDX1 in maintaining acinar cell identity, thus resisting the formation of PanIN-derived PDA. Upon neoplastic transformation, the role of PDX1 changes from tumor suppressive to oncogenic. Interestingly, subsets of malignant cells lose PDX1 expression while undergoing EMT and PDX1 loss is associated with poor outcome. This stage-specific functionality arises from profound shifts in PDX1 chromatin occupancy from acinar cells to PDA. In summary, we report distinct roles of PDX1 at different stages of PDA, suggesting that therapeutic approaches against this potential target need to account for its changing functions at different stages of carcinogenesis. These findings provide insight into the complexity of PDA pathogenesis and advocate a rigorous investigation of therapeutically tractable targets at distinct phases of PDA development and progression.
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| Overall design |
Examination of the effects of PDX1 binding on gene expression in the pancreatic cancer cell line NB490. We evaluated the effect of PDX1 binding by comparing gene expression
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| Contributor(s) |
Richard M, Roy N, Takeuchi KK, Ruggeri JM, Bailey P, Chang D, Li J, Leonhardt L, Puri S, Hoffman MT, Gao S, Halbrook CJ, Song Y, Ljungman M, Malik S, Wright CV, Dawson DW, Biankin AV, Hebrok M, Crawford HC |
| Citation(s) |
28087712 |
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| Submission date |
Dec 08, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Richard C McEachin |
| E-mail(s) |
mceachin@umich.edu
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| Organization name |
University of Michigan
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| Department |
DCM&B
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| Street address |
2800 Plymouth Road
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| City |
Ann Arbor |
| State/province |
United States |
| ZIP/Postal code |
48109 |
| Country |
USA |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (24)
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| This SubSeries is part of SuperSeries: |
| GSE91056 |
PDX1 dynamically regulates pancreatic ductal adenocarcinoma initiation and maintenance |
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| Relations |
| BioProject |
PRJNA356751 |
| SRA |
SRP094773 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE91052_WT_KO_FPKMs.xlsx |
6.0 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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