prikaz prve stranice dokumenta Proteomic Profiling of BRAFV600E Mutant Colon Cancer Cells Reveals the Involvement of Nucleophosmin/c-Myc Axis in Modulating the Response and Resistance to BRAF Inhibition by Vemurafenib
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Scientific paper - Original scientific paper
Proteomic Profiling of BRAFV600E Mutant Colon Cancer Cells Reveals the Involvement of Nucleophosmin/c-Myc Axis in Modulating the Response and Resistance to BRAF Inhibition by Vemurafenib
International Journal of Molecular Sciences, 22 (2021), 12; 6174. https://doi.org/10.3390/ijms22126174
Grbčić, Petra; Fučkar Čupić, Dora; Gamberi, Tania; Kraljević Pavelić, Sandra; Sedić, Mirela

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Grbčić, P., Fučkar Čupić, D., Gamberi, T., Kraljević Pavelić, S. & Sedić, M. (2021). Proteomic Profiling of BRAFV600E Mutant Colon Cancer Cells Reveals the Involvement of Nucleophosmin/c-Myc Axis in Modulating the Response and Resistance to BRAF Inhibition by Vemurafenib. International Journal of Molecular Sciences, 22. (12). doi: 10.3390/ijms22126174

Grbčić, Petra, et al. "Proteomic Profiling of BRAFV600E Mutant Colon Cancer Cells Reveals the Involvement of Nucleophosmin/c-Myc Axis in Modulating the Response and Resistance to BRAF Inhibition by Vemurafenib." International Journal of Molecular Sciences, vol. 22, no. 12, 2021. https://doi.org/10.3390/ijms22126174

Grbčić, Petra, Dora Fučkar Čupić, Tania Gamberi, Sandra Kraljević Pavelić and Mirela Sedić. "Proteomic Profiling of BRAFV600E Mutant Colon Cancer Cells Reveals the Involvement of Nucleophosmin/c-Myc Axis in Modulating the Response and Resistance to BRAF Inhibition by Vemurafenib." International Journal of Molecular Sciences 22, no. 12 (2021). https://doi.org/10.3390/ijms22126174

Grbčić, P., et al. (2021) 'Proteomic Profiling of BRAFV600E Mutant Colon Cancer Cells Reveals the Involvement of Nucleophosmin/c-Myc Axis in Modulating the Response and Resistance to BRAF Inhibition by Vemurafenib', International Journal of Molecular Sciences, 22(12). doi: 10.3390/ijms22126174

Grbčić P, Fučkar Čupić D, Gamberi T, Kraljević Pavelić S, Sedić M. Proteomic Profiling of BRAFV600E Mutant Colon Cancer Cells Reveals the Involvement of Nucleophosmin/c-Myc Axis in Modulating the Response and Resistance to BRAF Inhibition by Vemurafenib. International Journal of Molecular Sciences [Internet]. 2021 June 08 [cited 2024 May 06];22(12). doi: 10.3390/ijms22126174

P. Grbčić, D. Fučkar Čupić, T. Gamberi, S. Kraljević Pavelić and M. Sedić, "Proteomic Profiling of BRAFV600E Mutant Colon Cancer Cells Reveals the Involvement of Nucleophosmin/c-Myc Axis in Modulating the Response and Resistance to BRAF Inhibition by Vemurafenib", International Journal of Molecular Sciences, vol. 22, no. 12, June 2021. [Online]. Available at: https://urn.nsk.hr/urn:nbn:hr:184:027666. [Accessed: 06 May 2024]

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Metadata
Title (english)Proteomic Profiling of BRAFV600E Mutant Colon Cancer Cells Reveals the Involvement of Nucleophosmin/c-Myc Axis in Modulating the Response and Resistance to BRAF Inhibition by Vemurafenib
AuthorPetra Grbčić
AuthorDora Fučkar Čupić
AuthorTania Gamberi
AuthorSandra Kraljević Pavelić
AuthorMirela Sedić
Author's institutionUniversity of Rijeka
Faculty of Health Studies
Author's institutionUniversity of Rijeka
(Faculty of Biotechnology and Drug Development)
Author's institutionUniversity of Rijeka
Faculty of Medicine
(Department of General Pathology and Pathological Anatomy)
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Clinical Medical Sciences
Pathology
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Basic Medical Sciences
Human Genetics, Genomics and Proteomics
Abstract (english)
BRAFV600E mutations are found in approximately 10% of colorectal cancer patients and are associated with worse prognosis and poor outcomes with systemic therapies. The aim of this study was to identify novel druggable features of BRAFV600E-mutated colon cancer (CC) cells associated with the response and resistance to BRAFV600E inhibitor vemurafenib. Towards this aim, we carried out global proteomic profiling of BRAFV600E mutant vs. KRAS mutant/BRAF wild-type and double wild-type KRAS/BRAF CC cells followed by bioinformatics analyses. Validation of selected proteomic features was performed by immunohistochemistry and in silico using the TCGA database. We reveal an increased abundance and activity of nucleophosmin (NPM1) in BRAFV600E-mutated CC in vitro, in silico and in tumor tissues from colon adenocarcinoma patients and demonstrate the roles of NPM1 and its interaction partner c-Myc in conveying the resistance to vemurafenib. Pharmacological inhibition of NPM1 effectively restored the sensitivity of vemurafenib-resistant BRAF-mutated CC cells by down-regulating c-Myc expression and activity and consequently suppressing its transcriptional targets RanBP1 and phosphoserine phosphatase that regulate centrosome duplication and serine biosynthesis, respectively. Altogether, findings from this study suggest that the NPM1/c-Myc axis could represent a promising therapeutic target to thwart resistance to vemurafenib in BRAF-mutated CC.
Keywords (english)
Languageenglish
Publication typeScientific paper - Original scientific paper
Publication statusPublished
Peer reviewPeer review - international
Publication versionPublished version
Journal titleInternational Journal of Molecular Sciences
Numberingvol. 22, no. 12, 6174
e-ISSN1422-0067
DOIhttps://doi.org/10.3390/ijms22126174
URN:NBNurn:nbn:hr:184:027666
Publication2021-06-08
ProjectNumber: IP-2018-01-3900
Title (croatian): Rasvijetljavanje mehanizama rezistencije na terapiju raka debelog crijeva sa mutacijom BRAF pomoću integriranog -omics pristupa
Acronym: BRAFCON
Leader: Mirela Sedić
Jurisdiction: Croatia
Funding stream: IP
Document URLhttps://www.mdpi.com/1422-0067/22/12/6174
Type of resourceText
Access conditionsOpen access
Terms of useLicence Attribution 4.0 International (CC BY 4.0) icon
Created on2021-09-17 09:45:48