| First Author | Yong KJ | Year | 2016 |
| Journal | Sci Transl Med | Volume | 8 |
| Issue | 350 | Pages | 350ra104 |
| PubMed ID | 27488898 | Mgi Jnum | J:249432 |
| Mgi Id | MGI:5922950 | Doi | 10.1126/scitranslmed.aad6066 |
| Citation | Yong KJ, et al. (2016) Targeted BMI1 inhibition impairs tumor growth in lung adenocarcinomas with low CEBPalpha expression. Sci Transl Med 8(350):350ra104 |
| abstractText | Lung cancer is the most common cause of cancer deaths. The expression of the transcription factor C/EBPalpha (CCAAT/enhancer binding protein alpha) is frequently lost in non-small cell lung cancer, but the mechanisms by which C/EBPalpha suppresses tumor formation are not fully understood. In addition, no pharmacological therapy is available to specifically target C/EBPalpha expression. We discovered a subset of pulmonary adenocarcinoma patients in whom negative/low C/EBPalpha expression and positive expression of the oncogenic protein BMI1 (B lymphoma Mo-MLV insertion region 1 homolog) have prognostic value. We also generated a lung-specific mouse model of C/EBPalpha deletion that develops lung adenocarcinomas, which are prevented by Bmi1 haploinsufficiency. BMI1 activity is required for both tumor initiation and maintenance in the C/EBPalpha-null background, and pharmacological inhibition of BMI1 exhibits antitumor effects in both murine and human adenocarcinoma lines. Overall, we show that C/EBPalpha is a tumor suppressor in lung cancer and that BMI1 is required for the oncogenic process downstream of C/EBPalpha loss. Therefore, anti-BMI1 pharmacological inhibition may offer a therapeutic benefit for lung cancer patients with low expression of C/EBPalpha and high BMI1. |
