| First Author | Wang Y | Year | 2017 |
| Journal | Int J Biol Sci | Volume | 13 |
| Issue | 5 | Pages | 652-659 |
| PubMed ID | 28539837 | Mgi Jnum | J:265014 |
| Mgi Id | MGI:6198835 | Doi | 10.7150/ijbs.19108 |
| Citation | Wang Y, et al. (2017) Ezh2 Acts as a Tumor Suppressor in Kras-driven Lung Adenocarcinoma. Int J Biol Sci 13(5):652-659 |
| abstractText | Previous studies have suggested that enhancer zeste homolog 2 (Ezh2), a histone methyltransferase subunit of polycomb repressive complex 2 (PRC2), acts as an oncogene in lung adenocarcinoma (ADC) development. However, we found that in human lung ADC samples, deletion and mutations of EZH2 were also frequently present, with 14% of patients harboring loss-of-function EZH2 alterations. To explore the effect of Ezh2 loss on lung tumor formation, lung epithelial Ezh2 gene was deleted in Kras-driven lung ADC mouse model. Unexpectedly, Ezh2 loss dramatically promoted Kras-driven ADC formation. Kras(G12D/+);Ezh2(fl/fl) mice exhibited shorter lifespan, more tumor lesions and higher tumor burden than Kras(G12D/+) mice, suggesting the tumor-suppressive role of Ezh2 in Kras-driven ADCs. Mechanistically, Ezh2 loss amplified Akt and ERK activation through de-repressing its target insulin-like growth factor 1 (Igf1). Additionally, Ezh2 loss cooperated with Kras mutation to exacerbate the inflammatory response, as shown by massive macrophage and neutrophil infiltrates, as well as a marked increase in tumor-associated cytokines such as IL-6 and TNF-alpha. Taken together, our findings revealed the tumor suppressive function of Ezh2 in Kras-driven ADCs, underlining the importance of revaluating the application of EZH2 inhibitors in a variety of cancers. |
