| First Author | Mathsyaraja H | Year | 2021 |
| Journal | Elife | Volume | 10 |
| PubMed ID | 34236315 | Mgi Jnum | J:308027 |
| Mgi Id | MGI:6727686 | Doi | 10.7554/eLife.64212 |
| Citation | Mathsyaraja H, et al. (2021) Loss of MGA repression mediated by an atypical polycomb complex promotes tumor progression and invasiveness. Elife 10:e64212 |
| abstractText | MGA, a transcription factor and member of the MYC network, is mutated or deleted in a broad spectrum of malignancies. As a critical test of a tumor suppressive role, we inactivated Mga in two mouse models of non-small cell lung cancer using a CRISPR-based approach. MGA loss significantly accelerated tumor growth in both models and led to de-repression of non-canonical Polycomb ncPRC1.6 targets, including genes involved in metastasis and meiosis. Moreover, MGA deletion in human lung adenocarcinoma lines augmented invasive capabilities. We further show that MGA-MAX, E2F6, and L3MBTL2 co-occupy thousands of promoters and that MGA stabilizes these ncPRC1.6 subunits. Lastly, we report that MGA loss also induces a pro-growth effect in human colon organoids. Our studies establish MGA as a bona fide tumor suppressor in vivo and suggest a tumor suppressive mechanism in adenocarcinomas resulting from widespread transcriptional attenuation of MYC and E2F target genes mediated by MGA-MAX associated with a non-canonical Polycomb complex. |
