ArticleJournal of translational medicine2024
Recycling machinery of integrin coupled with focal adhesion turnover via RAB11-UNC13D-FAK axis for migration of pancreatic cancer cells.
Article in Journal of translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Pathogenic mechanism of Eimeria tenella EtMIC2 promotes Eimeria tenella invasion and inhibits host cell apoptosis through binding to the ITGAV receptor.Poultry science · 2026Article
- Large-scale and high-resolution mass spectrometry-based proteomics defines molecular subtypes of nasopharyngeal carcinoma for therapeutic targeting.Signal transduction and targeted therapy · 2026Article
- Integrins in cancer: insights into mechanisms and therapeutic potential.Cell communication and signaling : CCS · 2026Review
- Single-cell analysis of UNC13D-mediated immune and dedifferentiation heterogeneity in acute myeloid leukemia and development of a prognostic model.Translational cancer research · 2026Article
- Semaphorin 5A modulates focal adhesion pathway and lamellipodia formation in melanoma.Cell communication and signaling : CCS · 2025Article
- Constructing a Pan-Cancer Prognostic Model via Machine Learning Based on Immunogenic Cell Death Genes and Identifying NT5E as a Biomarker in Head and Neck Cancer.Current issues in molecular biology · 2025Article
- Integrins from extracellular vesicles as players in tumor microenvironment and metastasis.Cancer metastasis reviews · 2025Review
- Anoikis resistance in Cancer: Mechanisms, therapeutic strategies, potential targets, and models for enhanced understanding.Cancer letters · 2025Review
- Focal adhesion in the tumour metastasis: from molecular mechanisms to therapeutic targets.Biomarker research · 2025Review
- Functional role of UNC13D in immune diseases and its therapeutic applications.Frontiers in immunology · 2024Review
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Authors and funding
10 authors.
Funding
Abstract
backgroundRecycling of integrin via endosomal vesicles is critical for the migration of cancer cells, which leads to the metastasis of pancreatic cancer and devastating cancer-related death. So, new diagnostic and therapeutic molecules which target the recycling of endosomal vesicles need to be developed.
methodsPublic databases including TCGA, ICGC, GSE21501, GSE28735, and GENT are analyzed to derive diagnostic and therapeutic targets. To reveal biological roles and underlying mechanisms of molecular targets, various molecular biological experiments were conducted.
resultsFirst, we identified UNC13D's overexpression in patients with pancreatic cancer (n = 824) and its prognostic significance and high hazard ratio (HR) in four independent pancreatic cancer cohorts (TCGA, n = 178, p = 0.014, HR = 3.629; ICGC, n = 91, p = 0.000, HR = 4.362; GSE21501, n = 102, p = 0.002, HR = 2.339; GSE28735, n = 45, p = 0.022, HR = 2.681). Additionally, its expression is associated with the clinicopathological progression of pancreatic cancer. Further biological studies have shown that UNC13D regulates the migration of pancreatic cancer cells by coupling the exocytosis of recycling endosomes with focal adhesion turnover via the regulation of FAK phosphorylation. Immunoprecipitation and immunocytochemistry showed the formation of the RAB11-UNC13D-FAK axis in endosomes during integrin recycling. We observed that UNC13D directly interacted with the FERM domain of FAK and regulated FAK phosphorylation in a calcium-dependent manner. Finally, we found co-expression of UNC13D and FAK showed the poorest survival (TCGA, p = 0.000; ICGC, p = 0.036; GSE28735, p = 0.006).
conclusionsWe highlight that UNC13D, a novel prognostic factor, promotes pancreatic cancer progression by coupling integrin recycling with focal adhesion turnover via the RAB11-UNC13D-FAK axis for the migration of pancreatic cancer cells.
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