{"doi":"10.1016/j.celrep.2025.115315","title":"TGF-β1-mediated intercellular signaling fuels cooperative cellular invasion","abstract":"Intratumoral heterogeneity drives cancer progression and influences treatment outcomes. The mechanisms underlying how cellular subpopulations communicate and cooperate to impact progression remain largely unknown. Here, we use collective invasion as a model to deconstruct processes underlying non-small cell lung cancer subpopulation cooperation. We reveal that collectively invading packs consist of heterogeneously cycling and non-cycling subpopulations using distinct pathways. We demonstrate that the follower subpopulation secretes transforming growth factor beta one (TGF-β1) to stimulate divergent subpopulation responses-including proliferation, pack cohesion, and JAG1-dependent invasion-depending on cellular context. While isolated followers maintain proliferation in response to TGF-β1, isolated leaders enter a quiescence-like cellular state. In contrast, leaders within a heterogeneous population sustain proliferation to maintain subpopulation proportions. In vivo, both leader and follower subpopulations are necessary for macro-metastatic disease progression. Taken together, these findings highlight that intercellular communication preserves tumor cell heterogeneity and promotes collective behaviors such as invasion and tumor progression.","journal":"Cell Reports","year":2025,"id":517909,"datarank":0.31191623125197543,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"self_citation_contribution":0.31191623125197543,"citation_network_contribution":0.0,"self_endowment_contribution":0.31191623125197543,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9536,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":524026,"name":"Brian Pedro","orcid":"0000-0003-1898-3458","position":1,"is_corresponding":false},{"id":582376,"name":"Sergei Bombin","orcid":"0000-0002-8333-932X","position":2,"is_corresponding":false},{"id":1258056,"name":"Veronika Y Matsuk","orcid":null,"position":3,"is_corresponding":false},{"id":517680,"name":"Isaac E. Robinson","orcid":"0000-0002-6773-6755","position":4,"is_corresponding":false},{"id":1021068,"name":"Sarah Webster","orcid":"0000-0002-9716-3249","position":5,"is_corresponding":false},{"id":1385349,"name":"Landon J. Marcus","orcid":null,"position":6,"is_corresponding":false},{"id":275295,"name":"Emily R. Summerbell","orcid":"0000-0002-1336-1433","position":7,"is_corresponding":false},{"id":244967,"name":"Gregory K. Tharp","orcid":"0000-0003-3075-755X","position":8,"is_corresponding":false},{"id":373300,"name":"Christina M. Knippler","orcid":"0000-0003-3947-1830","position":9,"is_corresponding":false},{"id":741066,"name":"Pritha Bagchi","orcid":"0000-0001-7229-9476","position":10,"is_corresponding":false},{"id":1092973,"name":"Jeanne Kowalski-Muegge","orcid":null,"position":11,"is_corresponding":false},{"id":263877,"name":"H. Richard Johnston","orcid":"0000-0001-5668-1093","position":12,"is_corresponding":false},{"id":367593,"name":"Homa Ghalei","orcid":"0000-0003-0168-4654","position":13,"is_corresponding":false},{"id":524027,"name":"Paula M. Vertino","orcid":"0000-0001-6165-2019","position":14,"is_corresponding":false},{"id":275294,"name":"Janna K. Mouw","orcid":"0000-0002-9846-8466","position":15,"is_corresponding":false},{"id":275301,"name":"Adam I. Marcus","orcid":"0000-0003-0484-3569","position":16,"is_corresponding":false},{"id":813121,"name":"Tala O. Khatib","orcid":"0000-0003-3052-8474","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:49:04.756302Z","pmid":"39955775","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":[]}