EVI1 activates tumor-promoting transcriptional enhancers in pancreatic cancer
- Authors
- Kim, Hwa-Ryeon; Yim, Juhye; Yoo, Hye-Been; Lee, Seung Eon; Oh, Sumin; Jung, Sungju; Hwang, Chang-il; Shin, Dong-Myung; Kim, TaeSoo; Yoo, Kyung Hyun; Kim, You-Sun; Lee, Han-Woong; Roe, Jae-Seok
- Issue Date
- Jun-2021
- Publisher
- Oxford University Press (OUP)
- Citation
- NAR Cancer, v.3, no.2, pp 1 - 15
- Pages
- 15
- Journal Title
- NAR Cancer
- Volume
- 3
- Number
- 2
- Start Page
- 1
- End Page
- 15
- URI
- https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/151338
- DOI
- 10.1093/narcan/zcab023
- ISSN
- 2632-8674
- Abstract
- Cancer cells utilize epigenetic alterations to acquire autonomous capabilities for tumor maintenance. Here, we show that pancreatic ductal adenocarcinoma (PDA) cells utilize super-enhancers (SEs) to activate the transcription factor EVI1 (ecotropic viral integration site 1) gene, resulting in activation of an EVI1-dependent transcription program conferring PDA tumorigenesis. Our data indicate that SE is the vital cis-acting element to maintain aberrant EVI1 transcription in PDA cells. Consistent with disease progression and inferior survival outcomes of PDA patients, we further show that EVI1 upregulation is a major cause of aggressive tumor phenotypes. Specifically, EVI1 promotes anchorage-independent growth and motility in vitro and enhances tumor propagation in vivo. Mechanistically, EVI1-dependent activation of tumor-promoting gene expression programs through the stepwise configuration of the active enhancer chromatin attributes to these phenotypes. In sum, our findings support the premise that EVI1 is a crucial driver of oncogenic transcription programs in PDA cells. Further, we emphasize the instructive role of epigenetic aberrancy in establishing PDA tumorigenesis.
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