{"doi":"10.1016/j.celrep.2025.116701","title":"A cell-state axis underlying colonization in carcinomas with implications for metastasis risk prediction and interception","abstract":"Metastasis to the liver drives mortality in pancreatic ductal adenocarcinoma (PDAC), yet mechanisms of colonization remain unclear. Using genomic barcoding, we developed a clonal competition model under immune surveillance, isolating murine PDAC subclones with high or low liver-colonization potential. Combined transcriptome and chromatin-accessibility analyses revealed a distinct \"metastatic-potential axis,\" separate from the normal-to-PDAC and classical-basal axes. We established \"MetScore\" as a biomarker of this axis. MetScore distinguishes metastases from primary PDAC tumors in patients, predicts outcomes beyond classical-basal classifications, and generalizes across carcinoma subtypes, suggesting conserved colonization mechanisms. High-MetScore PDAC cells preferentially occupy immune cell-enriched niches, suggesting they remodel the metastatic microenvironment. Functional screening identified c-Fos as a positive mediator of colonization and a candidate anti-metastatic target. Collectively, we identify a cell-state axis underpinning PDAC liver colonization, introduce MetScore as a broadly applicable biomarker, and nominate actionable targets for peri-operative therapeutic intervention.","journal":"Cell Reports","year":2025,"id":4258,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.047,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-12-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":43295,"name":"Zijie Li","orcid":"0009-0001-2485-1980","position":1,"is_corresponding":false},{"id":43296,"name":"Rachel K. Dveirin","orcid":null,"position":2,"is_corresponding":false},{"id":55980,"name":"Jeff Lin","orcid":"0009-0004-2417-917X","position":3,"is_corresponding":false},{"id":43298,"name":"Weixiang Fang","orcid":"0000-0002-1152-7508","position":4,"is_corresponding":false},{"id":43299,"name":"Shihan Wu","orcid":null,"position":5,"is_corresponding":false},{"id":43300,"name":"James E. Forsmo","orcid":null,"position":6,"is_corresponding":false},{"id":43301,"name":"Hani Goodarzi","orcid":"0000-0002-9648-8949","position":7,"is_corresponding":false},{"id":11499,"name":"Elana J. Fertig","orcid":"0000-0003-3204-342X","position":8,"is_corresponding":false},{"id":43302,"name":"Reza Kalhor","orcid":"0000-0002-5558-7545","position":9,"is_corresponding":false},{"id":43303,"name":"Rachel Dveirin","orcid":"0000-0003-0453-503X","position":10,"is_corresponding":false},{"id":43304,"name":"Jessica Lin","orcid":null,"position":11,"is_corresponding":false},{"id":43294,"name":"Jesse S. Handler","orcid":"0000-0001-5444-3905","position":0,"is_corresponding":true}],"reference_count":87,"raw_metadata":null,"created_at":"2026-03-01T18:20:47.508186Z","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":[]}