prikaz prve stranice dokumenta Ezrin Inhibition Overcomes Acquired Resistance to Vemurafenib in BRAFV600E-Mutated Colon Cancer and Melanoma Cells In Vitro
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Scientific paper - Preliminary note / Short communication
Ezrin Inhibition Overcomes Acquired Resistance to Vemurafenib in BRAFV600E-Mutated Colon Cancer and Melanoma Cells In Vitro
International Journal of Molecular Sciences, 24 (2023); 1-25. https://doi.org/10.3390/ijms241612906
Car, Iris; Dittmann, Antje; Vasieva, Olga; Bočkor, Luka; Grbčić, Petra; Piteša, Nikolina; Klobučar, Marko; Kraljević Pavelić, Sandra; Sedić, Mirela

Institutional repository: Repository of the University of Rijeka, Faculty of Health Studies

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Car, I., Dittmann, A., Vasieva, O., Bočkor, L., Grbčić, P., Piteša, N. ... Sedić, M. (2023). Ezrin Inhibition Overcomes Acquired Resistance to Vemurafenib in BRAFV600E-Mutated Colon Cancer and Melanoma Cells In Vitro. International Journal of Molecular Sciences, 24., 1-25. doi: 10.3390/ijms241612906

Car, Iris, et al. "Ezrin Inhibition Overcomes Acquired Resistance to Vemurafenib in BRAFV600E-Mutated Colon Cancer and Melanoma Cells In Vitro." International Journal of Molecular Sciences, vol. 24, 2023, pp. 1-25. https://doi.org/10.3390/ijms241612906

Car, Iris, Antje Dittmann, Olga Vasieva, Luka Bočkor, Petra Grbčić, Nikolina Piteša, Marko Klobučar, Sandra Kraljević Pavelić and Mirela Sedić. "Ezrin Inhibition Overcomes Acquired Resistance to Vemurafenib in BRAFV600E-Mutated Colon Cancer and Melanoma Cells In Vitro." International Journal of Molecular Sciences 24 (2023): 1-25. https://doi.org/10.3390/ijms241612906

Car, I., et al. (2023) 'Ezrin Inhibition Overcomes Acquired Resistance to Vemurafenib in BRAFV600E-Mutated Colon Cancer and Melanoma Cells In Vitro', International Journal of Molecular Sciences, 24, pp. 1-25. doi: 10.3390/ijms241612906

Car I, Dittmann A, Vasieva O, Bočkor L, Grbčić P, Piteša N, and sur.. Ezrin Inhibition Overcomes Acquired Resistance to Vemurafenib in BRAFV600E-Mutated Colon Cancer and Melanoma Cells In Vitro. International Journal of Molecular Sciences [Internet]. 2023 August 17 [cited 2024 December 01];24:1-25. doi: 10.3390/ijms241612906

I. Car, et al., "Ezrin Inhibition Overcomes Acquired Resistance to Vemurafenib in BRAFV600E-Mutated Colon Cancer and Melanoma Cells In Vitro", International Journal of Molecular Sciences, vol. 24, pp. 1-25, August 2023. [Online]. Available at: https://urn.nsk.hr/urn:nbn:hr:184:018325. [Accessed: 01 December 2024]

Metadata
Title (english)Ezrin Inhibition Overcomes Acquired Resistance to Vemurafenib in BRAFV600E-Mutated Colon Cancer and Melanoma Cells In Vitro
AuthorIris Car
AuthorAntje Dittmann
AuthorOlga Vasieva
AuthorLuka Bočkor
AuthorPetra Grbčić
AuthorNikolina Piteša
AuthorMarko Klobučar
AuthorSandra Kraljević Pavelić
AuthorMirela Sedić
Author's institutionUniversity of Rijeka
Faculty of Health Studies
(Department of Basic Medical Sciences)
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Basic Medical Sciences
Human Genetics, Genomics and Proteomics
Abstract (english)
Despite the advancements in targeted therapy for BRAFV600E-mutated metastatic colorectal cancer (mCRC), the development of resistance to BRAFV600E inhibition limits the response rate and durability of the treatment. Better understanding of the resistance mechanisms to BRAF inhibitors will facilitate the design of novel pharmacological strategies for BRAF-mutated mCRC. The aim of this study was to identify novel protein candidates involved in acquired resistance to BRAFV600E inhibitor vemurafenib in BRAFV600E-mutated colon cancer cells using an integrated proteomics approach. Bioinformatic analysis of obtained proteomics data indicated actin-cytoskeleton linker protein ezrin as a highly ranked protein significantly associated with vemurafenib resistance whose overexpression in the resistant cells was additionally confirmed at the gene and protein level. Ezrin inhibition by NSC305787 increased anti-proliferative and pro-apoptotic effects of vemurafenib in the resistant cells in an additive manner, which was accompanied by downregulation of CD44 expression and inhibition of AKT/c-Myc activities. We also detected an increased ezrin expression in vemurafenib-resistant melanoma cells harbouring the BRAFV600E mutation. Importantly, ezrin inhibition potentiated anti-proliferative and pro-apoptotic effects of vemurafenib in the resistant melanoma cells in a synergistic manner. Altogether, our study suggests a role of ezrin in acquired resistance to vemurafenib in colon cancer and melanoma cells carrying the BRAFV600E mutation and supports further pre-clinical and clinical studies to explore the benefits of combined BRAF inhibitors and actin-targeting drugs as a potential therapeutic approach for BRAFV600E-mutated cancers.
Keywords (english)
Languageenglish
Publication typeScientific paper - Preliminary note / Short communication
Publication statusPublished
Peer reviewPeer review
Publication versionPublished version
Journal titleInternational Journal of Molecular Sciences
Numberingvol. 24, pp. 1-25
p-ISSN1661-6596
e-ISSN1422-0067
DOIhttps://doi.org/10.3390/ijms241612906
URN:NBNurn:nbn:hr:184:018325
Publication2023-08-17
Type of resourceText
Access conditionsOpen access
Terms of useLicence In copyright icon
Created on2023-08-21 06:40:23