{"doi":"10.1073/pnas.1914294117","title":"A mode of cell adhesion and migration facilitated by CD44-dependent microtentacles","abstract":"The structure and mechanics of many connective tissues are dictated by a collagen-rich extracellular matrix (ECM), where collagen fibers provide topological cues that direct cell migration. However, comparatively little is known about how cells navigate the hyaluronic acid (HA)-rich, nanoporous ECM of the brain, a problem with fundamental implications for development, inflammation, and tumor invasion. Here, we demonstrate that glioblastoma cells adhere to and invade HA-rich matrix using microtentacles (McTNs), which extend tens of micrometers from the cell body and are distinct from filopodia. We observe these structures in continuous culture models and primary patient-derived tumor cells, as well as in synthetic HA matrix and organotypic brain slices. High-magnification and superresolution imaging reveals McTNs are dynamic, CD44-coated tubular protrusions containing microtubules and actin filaments, which respectively drive McTN extension and retraction. Molecular mechanistic studies reveal that McTNs are stabilized by an interplay between microtubule-driven protrusion, actomyosin-driven retraction, and CD44-mediated adhesion, where adhesive and cytoskeletal components are mechanistically coupled by an IQGAP1-CLIP170 complex. McTNs represent a previously unappreciated mechanism through which cells engage nanoporous HA matrix and may represent an important molecular target in physiology and disease.","journal":"Proceedings of the National Academy of Sciences","year":2020,"id":54738,"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":100,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9504,"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":283560,"name":"Poojan Shukla","orcid":null,"position":1,"is_corresponding":false},{"id":283561,"name":"Kelsey S. Springer","orcid":null,"position":2,"is_corresponding":false},{"id":281803,"name":"Stacey Lee","orcid":"0000-0001-5645-8449","position":3,"is_corresponding":false},{"id":281804,"name":"Jason D. Coombes","orcid":"0000-0002-5601-8977","position":4,"is_corresponding":false},{"id":281805,"name":"Carina K Choy","orcid":"0000-0001-5418-3218","position":5,"is_corresponding":false},{"id":127788,"name":"Samuel J. Kenny","orcid":null,"position":6,"is_corresponding":false},{"id":218681,"name":"Ke Xu","orcid":"0000-0002-2788-194X","position":7,"is_corresponding":false},{"id":267986,"name":"Sanjay Kumar","orcid":"0000-0002-9996-4883","position":8,"is_corresponding":false},{"id":281802,"name":"Kayla J. Wolf","orcid":"0000-0001-6990-0283","position":0,"is_corresponding":true}],"reference_count":77,"raw_metadata":null,"created_at":"2026-07-18T21:04:14.743014Z","pmid":"32381732","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":[]}