| Autor: |
Haritha Mathsyaraja, Jonathen Catchpole, Brian Freie, Emily Eastwood, Ekaterina Babaeva, Michael Geuenich, Pei Feng Cheng, Jessica Ayers, Ming Yu, Nan Wu, Sitapriya Moorthi, Kumud R Poudel, Amanda Koehne, William Grady, A McGarry Houghton, Alice H Berger, Yuzuru Shiio, David MacPherson, Robert N Eisenman |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
eLife, Vol 10 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2050-084X |
| DOI: |
10.7554/eLife.64212 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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