Arid1a restrains Kras-dependent changes in acinar cell identity Journal Article
| Authors: | Livshits, G.; Alonso-Curbelo, D.; Morris, J. P. 4th; Koche, R.; Saborowski, M.; Wilkinson, J. E.; Lowe, S. W. |
| Article Title: | Arid1a restrains Kras-dependent changes in acinar cell identity |
| Abstract: | Mutations in members of the SWI/SNF chromatin remodeling family are common events in cancer, but the mechanisms whereby disruption of SWI/SNF components alters tumorigenesis remain poorly understood. To model the effect of loss of function mutations in the SWI/SNF subunit Arid1a in pancreatic ductal adenocarcinoma (PDAC) initiation, we directed shRNA triggered, inducible and reversible suppression of Arid1a to the mouse pancreas in the setting of oncogenic KrasG12D. Arid1a cooperates with Kras in the adult pancreas as postnatal silencing of Arid1a following sustained KrasG12D expression induces rapid and irreversible reprogramming of acinar cells into mucinous PDAC precursor lesions. In contrast, Arid1a silencing during embryogenesis, concurrent with KrasG12D activation, leads to retention of acinar cell fate. Together, our results demonstrate Arid1a as a critical modulator of Kras-dependent changes in acinar cell identity, and underscore an unanticipated influence of timing and genetic context on the effects of SWI/SNF complex alterations in epithelial tumorigenesis. © Livshits et al. |
| Journal Title: | eLife |
| Volume: | 7 |
| ISSN: | 2050-084X |
| Publisher: | eLife Sciences Publications Ltd. |
| Date Published: | 2018-07-17 |
| Start Page: | e35216 |
| Language: | English |
| DOI: | 10.7554/eLife.35216 |
| PROVIDER: | scopus |
| PMCID: | PMC6050044 |
| PUBMED: | 30014851 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 October 2018 -- Source: Scopus |
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