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YAP Signaling Regulates the Cellular Uptake and Therapeutic Effect of Nanoparticles

M. Cassani, S. Fernandes, J. Oliver-De La Cruz, H. Durikova, J. Vrbsky, M. Patočka, V. Hegrova, S. Klimovic, J. Pribyl, D. Debellis, P. Skladal, F. Cavalieri, F. Caruso, G. Forte

. 2024 ; 11 (2) : e2302965. [pub] 20231109

Language English Country Germany

Document type Journal Article

Persistent link   https://www.medvik.cz/link/bmc24007805

Grant support
NU23J-08-00035 Ministerstvo Zdravotnictví Ceské Republiky
800924 H2020 Marie Skłodowska-Curie Actions
CZ.02.1.01/0.0/0.0/18_046/0015974 European Regional Development Fund
CZ.02.1.01/0.0/0.0/16_019/0000868 European Regional Development Fund
CZ.02.1.01/0.0/0.0/15_003/0000492 European Regional Development Fund

Interactions between living cells and nanoparticles are extensively studied to enhance the delivery of therapeutics. Nanoparticles size, shape, stiffness, and surface charge are regarded as the main features able to control the fate of cell-nanoparticle interactions. However, the clinical translation of nanotherapies has so far been limited, and there is a need to better understand the biology of cell-nanoparticle interactions. This study investigates the role of cellular mechanosensitive components in cell-nanoparticle interactions. It is demonstrated that the genetic and pharmacologic inhibition of yes-associated protein (YAP), a key component of cancer cell mechanosensing apparatus and Hippo pathway effector, improves nanoparticle internalization in triple-negative breast cancer cells regardless of nanoparticle properties or substrate characteristics. This process occurs through YAP-dependent regulation of endocytic pathways, cell mechanics, and membrane organization. Hence, the study proposes targeting YAP may sensitize triple-negative breast cancer cells to chemotherapy and increase the selectivity of nanotherapy.

References provided by Crossref.org

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$a Interactions between living cells and nanoparticles are extensively studied to enhance the delivery of therapeutics. Nanoparticles size, shape, stiffness, and surface charge are regarded as the main features able to control the fate of cell-nanoparticle interactions. However, the clinical translation of nanotherapies has so far been limited, and there is a need to better understand the biology of cell-nanoparticle interactions. This study investigates the role of cellular mechanosensitive components in cell-nanoparticle interactions. It is demonstrated that the genetic and pharmacologic inhibition of yes-associated protein (YAP), a key component of cancer cell mechanosensing apparatus and Hippo pathway effector, improves nanoparticle internalization in triple-negative breast cancer cells regardless of nanoparticle properties or substrate characteristics. This process occurs through YAP-dependent regulation of endocytic pathways, cell mechanics, and membrane organization. Hence, the study proposes targeting YAP may sensitize triple-negative breast cancer cells to chemotherapy and increase the selectivity of nanotherapy.
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