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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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. i 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, br. 12, 2021. https://doi.org/10.3390/ijms22126174

Grbčić, Petra, Dora Fučkar Čupić, Tania Gamberi, Sandra Kraljević Pavelić i 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, br. 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]. 08.06.2021. [pristupljeno 17.11.2024.];22(12). doi: 10.3390/ijms22126174

P. Grbčić, D. Fučkar Čupić, T. Gamberi, S. Kraljević Pavelić i 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, br. 12, Lipanj 2021. [Online]. Dostupno na: https://urn.nsk.hr/urn:nbn:hr:184:027666. [Citirano: 17.11.2024.]

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Naslov (engleski)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
AutorPetra Grbčić
AutorDora Fučkar Čupić
AutorTania Gamberi
AutorSandra Kraljević Pavelić
AutorMirela Sedić
Autorova ustanovaSveučilište u Rijeci
Fakultet zdravstvenih studija
Autorova ustanovaSveučilište u Rijeci
(Fakultet biotehnologije i razvoja lijekova)
Autorova ustanovaSveučilište u Rijeci
Medicinski fakultet
(Katedra za opću patologiju i patološku anatomiju)
Znanstveno / umjetničko
područje, polje i grana		BIOMEDICINA I ZDRAVSTVO
Kliničke medicinske znanosti
Patologija
Znanstveno / umjetničko
područje, polje i grana		BIOMEDICINA I ZDRAVSTVO
Temeljne medicinske znanosti
Genetika, genomika i proteomika čovjeka
Sažetak (engleski)
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.
Ključne riječi (engleski)
Jezikengleski
Vrsta publikacijeZnanstveni rad - Izvorni znanstveni rad
Status objaveObjavljen
Vrsta recenzijeRecenziran - međunarodna recenzija
Verzija publikacijeObjavljena verzija rada (izdavačev PDF)
Naslov časopisaInternational Journal of Molecular Sciences
Brojčani podacivol. 22, br. 12, 6174
e-ISSN1422-0067
DOIhttps://doi.org/10.3390/ijms22126174
URN:NBNurn:nbn:hr:184:027666
Datum objave publikacije2021-06-08
ProjektŠifra: IP-2018-01-3900
Naziv (hrvatski): Rasvijetljavanje mehanizama rezistencije na terapiju raka debelog crijeva sa mutacijom BRAF pomoću integriranog -omics pristupa
Kratica: BRAFCON
Voditelj: Mirela Sedić
Pravna nadležnost: Hrvatska
Financijer: HRZZ
Linija financiranja: IP
URL dokumentahttps://www.mdpi.com/1422-0067/22/12/6174
Vrsta resursaTekst
Prava pristupaOtvoreni pristup
Uvjeti korištenjaIkona licence Imenovanje 4.0 međunarodna (CC BY 4.0)
Datum i vrijeme pohrane2021-09-17 09:45:48