ITGB3-mediated uptake of small extracellular vesicles facilitates intercellular communication in breast cancer cells

Pedro Fuentes, Marta Sesé, Pedro J. Guijarro, Marta Emperador, Sara Sánchez-Redondo, Héctor Peinado, Stefan Hümmer () and Santiago Ramón y Cajal ()
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Pedro Fuentes: Translational Molecular Pathology, Vall d’Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona (UAB)
Marta Sesé: Translational Molecular Pathology, Vall d’Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona (UAB)
Pedro J. Guijarro: Translational Molecular Pathology, Vall d’Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona (UAB)
Marta Emperador: Translational Molecular Pathology, Vall d’Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona (UAB)
Sara Sánchez-Redondo: Microenvironment & Metastasis Group, Molecular Oncology Program, Spanish National Cancer Research Centre (CNIO)
Héctor Peinado: Microenvironment & Metastasis Group, Molecular Oncology Program, Spanish National Cancer Research Centre (CNIO)
Stefan Hümmer: Translational Molecular Pathology, Vall d’Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona (UAB)
Santiago Ramón y Cajal: Translational Molecular Pathology, Vall d’Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona (UAB)

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: Abstract Metastasis, the spread of malignant cells from a primary tumour to distant sites, causes 90% of cancer-related deaths. The integrin ITGB3 has been previously described to play an essential role in breast cancer metastasis, but the precise mechanisms remain undefined. We have now uncovered essential and thus far unknown roles of ITGB3 in vesicle uptake. The functional requirement for ITGB3 derives from its interactions with heparan sulfate proteoglycans (HSPGs) and the process of integrin endocytosis, allowing the capture of extracellular vesicles and their endocytosis-mediated internalization. Key for the function of ITGB3 is the interaction and activation of focal adhesion kinase (FAK), which is required for endocytosis of these vesicles. Thus, ITGB3 has a central role in intracellular communication via extracellular vesicles, proposed to be critical for cancer metastasis.

Date: 2020
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DOI: 10.1038/s41467-020-18081-9

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