{"doi":"10.1101/2025.05.22.655615","title":"Hyperglycemic state and fluid shear stress affect metastatic breast cancer cell migration via focal adhesion kinase","abstract":"Abstract We tested how the diabetes-related hyperglycemic condition affects the migration of highly metastatic triple-negative breast cancer (TNBC) cells, MDA-MB-231, under a physiological fluid shear environment. MDA-MB-231 cells displayed a significantly enhanced migratory behavior under a high glucose condition (25 mM) specifically when exposed to flow at 15 dyne/cm 2 shear stress. In contrast, the effect of fluid shear was marginal under low glucose (5 mM). Normal epithelial MCF-10A cells, on the other hand, showed increased migration by fluid shear under both low and high glucose conditions. The fluid shear-triggered MDA-MB-231 cell migration under high glucose was significantly abrogated by a focal adhesion kinase (FAK) inhibitor, supporting the mediatory role of FAK in MDA-MB-231 TNBC cell sensing of the high glucose-fluid shear environment during migration. The role of FAK was further demonstrated by the effects of FAK inhibitor on MDA-MB-231 cell migration in scratch wound healing and Boyden chamber migration assays. Our studies provide evidence that high glucose and fluid shear could jointly trigger MDA-MB-231 TNBC cell migration that requires FAK activity. These may provide improved mechanistic insights into how concurrent diabetes may impact the pro-metastatic behavior of breast cancer and suggest the impact of exploring FAK as a relevant therapeutic target.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":566805,"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":0.9614,"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":458441,"name":"Eunju Kim","orcid":"0000-0003-2235-470X","position":1,"is_corresponding":false},{"id":1413863,"name":"Taylor Boudreaux","orcid":null,"position":2,"is_corresponding":false},{"id":1471075,"name":"Osaira Ovando","orcid":null,"position":3,"is_corresponding":false},{"id":1471076,"name":"Stephanie Vielmas- Duarte","orcid":null,"position":4,"is_corresponding":false},{"id":1214876,"name":"Suyong Choi","orcid":"0000-0002-0978-306X","position":5,"is_corresponding":false},{"id":415311,"name":"Hamid Band","orcid":"0000-0002-4996-9002","position":6,"is_corresponding":false},{"id":1471077,"name":"Lanju Mei","orcid":null,"position":7,"is_corresponding":false},{"id":1298590,"name":"Diganta Dutta","orcid":null,"position":8,"is_corresponding":false},{"id":736229,"name":"Surabhi Chandra","orcid":"0000-0003-1403-2911","position":9,"is_corresponding":false},{"id":381461,"name":"Jung Yul Lim","orcid":"0000-0002-9409-7522","position":10,"is_corresponding":false},{"id":680760,"name":"Brandon D. Riehl","orcid":null,"position":0,"is_corresponding":true}],"reference_count":34,"raw_metadata":null,"created_at":"2026-07-19T02:56:40.491968Z","pmid":"40502165","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":[]}