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The role of fibronectin (FN) in tumorigenesis and malignant progression has been highly controversial. Cancerous FN plays a tumor-suppressive role, whereas it is pro-metastatic and associated with poor prognosis. Interestingly, FN matrix deposited in the tumor microenvironments (TMEs) promotes tumor progression but is paradoxically related to a better prognosis. Here, we justify how FN impacts tumor transformation and subsequently metastatic progression. Next, we try to reconcile and rationalize the seemingly conflicting roles of FN in cancer and TMEs. Finally, we propose future perspectives for potential FN-based therapeutic strategies.
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http://dx.doi.org/10.3390/cells9010027 | DOI Listing |
Cell Rep Med
September 2025
Biological Sciences Platform, Sunnybrook Research Institute, Toronto, ON, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada. Electronic address:
The success of immune checkpoint inhibitors is limited by multiple factors, including poor T cell infiltration and function within tumors, partly due to a dense extracellular matrix (ECM). Here, we investigate modulating the ECM by targeting integrin α5β1, a major fibronectin-binding and organizing integrin, to improve immunotherapy outcomes. Use of a function-blocking murinized α5β1 antibody reduces fibronectin fibril formation, enhances CD8 T cell transendothelial migration, increases vascular permeability, and decreases vessel-associated collagen.
View Article and Find Full Text PDFiScience
September 2025
Université de Strasbourg, INSERM, EFS Grand Est, BPPS UMR-S1255, FMTS, 67065 Strasbourg, France.
Platelet integrins, together with other platelet receptors, are known to control hemostasis and thrombosis but also metastatic progression. However, the impact of their exclusive but combined deficiency has never been tested in these processes. In a PF4Cre-β1/β3 mouse strain, we found that platelets were exclusively depleted of all integrins.
View Article and Find Full Text PDFNat Commun
August 2025
Curriculum in Bioinformatics and Computational Biology, University of North Carolina, Chapel Hill, NC, USA.
Osteoarthritis affects millions worldwide, yet effective treatments remain elusive due to poorly understood molecular mechanisms. While genome-wide association studies (GWAS) have identified hundreds of osteoarthritis-associated loci, identifying the genes impacted at each locus remains challenging. We investigate alternative splicing using RNA-sequencing data from 101 human chondrocyte samples treated with phosphate-buffered saline or fibronectin fragment, an osteoarthritis trigger.
View Article and Find Full Text PDFHereditas
August 2025
Department of Anesthesiology, Affiliated Hospital of Inner Mongolia Medical University, No.1 North Street, Huimin District, Hohhot, 010010, Inner Mongolia Autonomous Region, China.
Background: Colon adenocarcinoma (COAD) is a frequent digestive system malignancy with high mortality and poor prognosis. Transmembrane Channel-like 5 (TMC5) has been reported to play an oncological role in various cancers. However, the role and mechanism of TMC5 in COAD remain unclear.
View Article and Find Full Text PDFJ Ovarian Res
August 2025
Department of Woman and Child's Health and Public Health Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
Background: Ovarian cancer remains a major clinical challenge with more than 40.000 annual deaths in Europe and in the United States, highlighting the need for better diagnostic and therapeutic strategies. This study first presents an immunohistochemical evaluation of the extra-domains A and B containing fibronectin (EDA-FN, EDB-FN), fibroblast activation protein (FAP), and carcinoembryonic antigen (CEA) in ovarian cancer specimens.
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