| Autor: |
Ekaterina Babaeva, Kumud R. Poudel, David MacPherson, Emily Eastwood, Brian Freie, Yuzuru Shiio, Jonathen Catchpole, Haritha Mathsyaraja, Jessica Ayers, Amanda Koehne, William M. Grady, Pei Feng Cheng, A. McGarry Houghton, Michael Geuenich, Nan Wu, Ming Yu, Robert N. Eisenman |
| Rok vydání: |
2020 |
| Předmět: |
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| 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 atypical Polycomb PRC1.6, E2F and MYC-MAX targets. Similarly, MGA depletion in human lung adenocarcinoma lines augmented invasive capabilities. We further show that MGA, E2F6 and L3MBTL2 co-occupy thousands of promoters and that MGA stabilizes PRC1.6 subunits. Lastly, we report that MGA loss has also 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 targets mediated by an atypical Polycomb complex containing MGA-MAX dimers. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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