{"doi":"10.1101/2020.10.16.334714","title":"Loss of MGA mediated Polycomb repression promotes tumor progression and invasiveness","abstract":"ABSTRACT 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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":124110,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9572,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":569276,"name":"Jonathen Catchpole","orcid":null,"position":1,"is_corresponding":false},{"id":550528,"name":"Emily Eastwood","orcid":"0000-0002-8329-2090","position":2,"is_corresponding":false},{"id":569277,"name":"Ekaterina Babaeva","orcid":null,"position":3,"is_corresponding":false},{"id":295728,"name":"Michael Geuenich","orcid":"0000-0001-6772-7309","position":4,"is_corresponding":false},{"id":569278,"name":"Pei Cheng","orcid":null,"position":5,"is_corresponding":false},{"id":295727,"name":"Brian Freie","orcid":"0000-0003-1450-865X","position":6,"is_corresponding":false},{"id":568388,"name":"Jessica Ayers","orcid":"0000-0002-6909-8945","position":7,"is_corresponding":false},{"id":214890,"name":"Ming Yu","orcid":"0000-0001-8692-6135","position":8,"is_corresponding":false},{"id":568389,"name":"Nan Wu","orcid":"0000-0002-7401-4136","position":9,"is_corresponding":false},{"id":568390,"name":"Kumud R. Poudel","orcid":"0000-0001-8141-6216","position":10,"is_corresponding":false},{"id":364431,"name":"Amanda Koehne","orcid":"0000-0002-1397-6964","position":11,"is_corresponding":false},{"id":86847,"name":"William M. Grady","orcid":"0000-0002-0129-7809","position":12,"is_corresponding":false},{"id":232697,"name":"A. McGarry Houghton","orcid":"0000-0002-8970-3137","position":13,"is_corresponding":false},{"id":493588,"name":"Yuzuru Shiio","orcid":"0000-0002-3391-9086","position":14,"is_corresponding":false},{"id":251318,"name":"David MacPherson","orcid":"0000-0003-3729-907X","position":15,"is_corresponding":false},{"id":73077,"name":"Robert N. Eisenman","orcid":"0000-0002-0274-9846","position":16,"is_corresponding":false},{"id":295725,"name":"Haritha Mathsyaraja","orcid":"0000-0002-1021-4921","position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":null,"created_at":"2026-07-18T23:15:07.789881Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}