{"doi":"10.7554/elife.64212","title":"Loss of MGA repression mediated by an atypical polycomb complex promotes tumor progression and invasiveness","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 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.","journal":"eLife","year":2021,"id":156767,"datarank":1.322884767550354,"base_score":3.9889840465642745,"endowment":3.9889840465642745,"self_citation_contribution":0.5983476069846413,"citation_network_contribution":0.7245371605657126,"self_endowment_contribution":0.5983476069846413,"citer_contribution":0.7245371605657126,"corpus_percentile":null,"corpus_rank":null,"citation_count":53,"citer_count":55,"citers_with_citation_signal":36,"citers_with_endowment":36,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9524,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE161606","GSE161609","GSE161539","GSE161541","GSE161543","GSE175838"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","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":295727,"name":"Brian Freie","orcid":"0000-0003-1450-865X","position":2,"is_corresponding":false},{"id":550528,"name":"Emily Eastwood","orcid":"0000-0002-8329-2090","position":3,"is_corresponding":false},{"id":569277,"name":"Ekaterina Babaeva","orcid":null,"position":4,"is_corresponding":false},{"id":295728,"name":"Michael Geuenich","orcid":"0000-0001-6772-7309","position":5,"is_corresponding":false},{"id":569278,"name":"Pei Cheng","orcid":null,"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":580573,"name":"Sitapriya Moorthi","orcid":"0000-0001-6372-5170","position":10,"is_corresponding":false},{"id":568390,"name":"Kumud R. Poudel","orcid":"0000-0001-8141-6216","position":11,"is_corresponding":false},{"id":364431,"name":"Amanda Koehne","orcid":"0000-0002-1397-6964","position":12,"is_corresponding":false},{"id":86847,"name":"William M. Grady","orcid":"0000-0002-0129-7809","position":13,"is_corresponding":false},{"id":232697,"name":"A. McGarry Houghton","orcid":"0000-0002-8970-3137","position":14,"is_corresponding":false},{"id":79456,"name":"Alice H. Berger","orcid":"0000-0002-6538-2658","position":15,"is_corresponding":false},{"id":493588,"name":"Yuzuru Shiio","orcid":"0000-0002-3391-9086","position":16,"is_corresponding":false},{"id":251318,"name":"David MacPherson","orcid":"0000-0003-3729-907X","position":17,"is_corresponding":false},{"id":73077,"name":"Robert N. Eisenman","orcid":"0000-0002-0274-9846","position":18,"is_corresponding":false},{"id":295725,"name":"Haritha Mathsyaraja","orcid":"0000-0002-1021-4921","position":0,"is_corresponding":true}],"reference_count":75,"raw_metadata":null,"created_at":"2026-07-18T23:44:13.017332Z","pmid":"34236315","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":[]}