![[feed]](/style/images/feed-icon-14x14.png){kind=icon}
Tools
Tools
| Item Type: | Article |
|---|---|
| Title: | Polycomb repressive complex 2 is a barrier to KRAS-driven inflammation and epithelial-mesenchymal transition in non-small-cell lung cancer |
| Creators Name: | Serresi, M., Gargiulo, G., Proost, N., Siteur, B., Cesaroni, M., Koppens, M., Xie, H., Sutherland, K.D., Hulsman, D., Citterio, E., Orkin, S., Berns, A. and van Lohuizen, M. |
| Abstract: | 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 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 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. |
| Keywords: | Acetylation, Animal Disease Models, Cell Proliferation, Epithelial-Mesenchymal Transition, Histones, Inflammation, Non-Small-Cell Lung Carcinoma, Polycomb Repressive Complex 2, Proto-Oncogene Proteins p21(ras), Transgenic Mice, Animals, Mice |
| Source: | Cancer Cell |
| ISSN: | 1535-6108 |
| Publisher: | Cell Press / Elsevier |
| Volume: | 29 |
| Number: | 1 |
| Page Range: | 17-31 |
| Date: | 11 January 2016 |
| Additional Information: | Erratum in: Cancer Cell 29(2):241. |
| Official Publication: | https://doi.org/10.1016/j.ccell.2015.12.006 |
| PubMed: | View item in PubMed |
Repository Staff Only: item control page
