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| Status |
Public on Jan 15, 2016 |
| Title |
Epigenomic profiling of Non-small-cell Lung Cancer (NSCLC) cells with or without Eed |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
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| Summary |
Polycomb repressive complexes (PRC) are frequently implicated in human cancer acting either as oncogenes or tumor suppressors. Here we show that PRC2 is a critical regulator of Kras-driven non-small-cell lung cancer (NSCLC) progression. Modulation of PRC2 by either Ezh2 overexpression or Eed deletion enhances Kras-driven adenomagenesis and inflammation, respectively. Eed-loss-driven inflammation leads to massive macrophage recruitment and marked decline in tissue function. Additional Trp53 inactivation activates a cell autonomous epithelial-to-mesenchymal transition (EMT) program leading to an invasive mucinous adenocarcinoma. A switch between methylated/acetylated chromatin underlies the tumor phenotypic evolution, prominently involving genes controlled by Hippo/Wnt-signaling. Our observations in the mouse models were conserved in human cells. Importantly, PRC2 inactivation results in context-dependent phenotypic alterations, with implications for its therapeutic application.
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| Overall design |
We generated ChIP-seq from primary Kras;p53 (KP) cells in culture with and without Eed (KPE) and from KP primary tumors generated by injection of NSCLC into the tail vein. Mice were sacrificed on the onset of shortness of breath. We generated genome-wide expression profiles (RNA-seq) and Nuclease Accessibility (NA)-seq in primary KP and KPE tumor cells. NA-seq was also performed in A549 cells.
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| Contributor(s) |
Gargiulo G, Serresi M, Cesaroni M, de Rink I |
| Citation(s) |
26766588 |
| Submission date |
Sep 08, 2014 |
| Last update date |
May 15, 2019 |
| Contact name |
Gaetano Gargiulo |
| E-mail(s) |
gaetano.gargiulo@mdc-berlin.de
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| Organization name |
Max Delbrüch Center
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| Department |
Molecular Oncology
|
| Street address |
Robert-Rössle-Straße 10
|
| City |
Berlin |
| ZIP/Postal code |
13125 |
| Country |
Germany |
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| Platforms (3) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (31)
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| Relations |
| BioProject |
PRJNA260490 |
| SRA |
SRP046306 |
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