{"doi":"10.1002/cm.21926","title":"Exploring the potential role of palladin in modulating human <scp>CAF</scp> / <scp>ECM</scp> functional units","abstract":"Fibroblasts, crucial for maintaining tissue homeostasis, significantly shape the tumor microenvironment (TME). In pancreatic cancer, a highly aggressive malignancy, cancer-associated fibroblast (CAF)/extracellular matrix (ECM) units dominate the TME, influencing tumor initiation, progression, and treatment responses. Palladin, an actin-associated protein, is vital for fibroblast structural integrity and activation, playing a key role in CAF/ECM functionality. Palladin interacts with cytoskeletal proteins such as alpha-actinin (α-Act) and can therefore regulate other proteins like syndecans, modulating cytoskeletal features, cell adhesion, integrin recycling, and signaling. In this review, we propose that targeting the palladin/α-Act/syndecan interaction network could modulate CAF/ECM units, potentially shifting the TME from a tumor-promoting to a tumor-suppressive state. In silico data and reported studies to suggest that stabilizing palladin-α-Act interactions, via excess palladin, influences syndecan functions; potentially modulating integrin endocytosis via syndecan engagement with protein kinase C alpha as opposed to syndecan binding to α-Act. This mechanism can then affect the distribution of active α5β1-integrin between the plasma membrane and known intracellular vesicular compartments, thereby influencing the tumor-suppressive versus tumor-promoting functions of CAF/ECM units. Understanding these interactions offers likely future therapeutic avenues for stroma normalization in pancreatic and other cancers, aiming to inhibit tumor progression and improve future treatment outcomes.","journal":"Cytoskeleton","year":2024,"id":481330,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9544,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1320988,"name":"Sérgio Alexandre Alcântara dos Santos","orcid":"0000-0002-1375-1634","position":1,"is_corresponding":false},{"id":965870,"name":"Mark Andrake","orcid":"0000-0003-2957-4350","position":2,"is_corresponding":false},{"id":241835,"name":"Janusz Franco‐Barraza","orcid":"0000-0003-3652-5311","position":3,"is_corresponding":false},{"id":56679,"name":"Roland L. Dunbrack","orcid":"0000-0001-7674-6667","position":4,"is_corresponding":false},{"id":103959,"name":"Edna Cukierman","orcid":"0000-0002-1452-9576","position":5,"is_corresponding":false},{"id":1321388,"name":"Aleksandr Dolskii","orcid":null,"position":0,"is_corresponding":true}],"reference_count":123,"raw_metadata":null,"created_at":"2026-07-19T02:07:06.225103Z","pmid":"39239855","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":[]}