{"doi":"10.17615/5ptk-cs32","title":"Tumor Cell-Driven Extracellular Matrix Remodeling Drives Haptotaxis during Metastatic Progression","abstract":"Fibronectin (FN) is a major component of the tumor microenvironment, but its role in promoting metastasis is incompletely understood. Here we show that FN gradients elicit directional movement of breast cancer cells, in vitro and in vivo. Haptotaxis on FN gradients requires direct interaction between α5β1 integrin and Mena, an actin regulator, and involves increases in focal complex signaling and tumor-cell-mediated extracellular matrix (ECM) remodeling. Compared to Mena, higher levels of the pro-metastatic MenaINV isoform associate with α5, which enables 3D haptotaxis of tumor cells towards the high FN concentrations typically present in perivascular space and in the periphery of breast tumor tissue. MenaINV and FN levels were correlated in two breast cancer cohorts, and high levels of MenaINV were significantly associated with increased tumor recurrence as well as decreased patient survival. Our results identify a novel tumor-cell-intrinsic mechanism that promotes metastasis through ECM remodeling and ECM guided directional migration.","journal":"UNC Libraries","year":2020,"id":144365,"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":0.9548,"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":612848,"name":"Kari B. Wisinski","orcid":"0000-0003-3535-0652","position":1,"is_corresponding":false},{"id":613440,"name":"Jeff Wyckoff","orcid":null,"position":2,"is_corresponding":false},{"id":612849,"name":"Oliver Jonas","orcid":"0000-0003-2512-2007","position":3,"is_corresponding":false},{"id":98827,"name":"Liliane C. Broye","orcid":null,"position":4,"is_corresponding":false},{"id":612850,"name":"Maaike Cima","orcid":"0000-0002-3458-5276","position":5,"is_corresponding":false},{"id":453521,"name":"James E. Bear","orcid":"0000-0002-8489-996X","position":6,"is_corresponding":false},{"id":612851,"name":"Bruna C. Guido","orcid":"0000-0001-6397-1259","position":7,"is_corresponding":false},{"id":612852,"name":"Duanduan Ma","orcid":"0000-0002-4753-0813","position":8,"is_corresponding":false},{"id":531398,"name":"Sreeja B. Asokan","orcid":null,"position":9,"is_corresponding":false},{"id":613441,"name":"Whittaker, Charlie","orcid":null,"position":10,"is_corresponding":false},{"id":434781,"name":"Frank B. Gertler","orcid":null,"position":11,"is_corresponding":false},{"id":613442,"name":"Daisy Riquelme","orcid":null,"position":12,"is_corresponding":false},{"id":271360,"name":"John M. Lamar","orcid":"0000-0001-5406-8391","position":13,"is_corresponding":false},{"id":62838,"name":"Richard O. Hynes","orcid":"0000-0001-7603-8396","position":14,"is_corresponding":false},{"id":248018,"name":"Madeleine J. Oudin","orcid":"0000-0001-6988-4260","position":15,"is_corresponding":false},{"id":40706,"name":"Robert Langer","orcid":"0000-0003-4255-0492","position":16,"is_corresponding":false},{"id":19320,"name":"Douglas A. Lauffenburger","orcid":"0000-0002-0050-989X","position":17,"is_corresponding":false},{"id":609262,"name":"Patricia J. KEELY","orcid":null,"position":18,"is_corresponding":false},{"id":277246,"name":"Tatsiana Kosciuk","orcid":"0000-0001-8509-973X","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:17:45.339291Z","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":[]}