Please use this identifier to cite or link to this item: http://hdl.handle.net/10773/27792
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dc.contributor.authorSantos, Mafaldapt_PT
dc.contributor.authorPereira, Patrícia M.pt_PT
dc.contributor.authorVaranda, A. Sofiapt_PT
dc.contributor.authorCarvalho, Joanapt_PT
dc.contributor.authorAzevedo, Mafaldapt_PT
dc.contributor.authorMateus, Denisa D.pt_PT
dc.contributor.authorMendes, Nunopt_PT
dc.contributor.authorOliveira, Patríciapt_PT
dc.contributor.authorTrindade, Fábiopt_PT
dc.contributor.authorPinto, Marta Teixeirapt_PT
dc.contributor.authorBordeira-Carriço, Renatapt_PT
dc.contributor.authorCarneiro, Fátimapt_PT
dc.contributor.authorVitorino, Ruipt_PT
dc.contributor.authorOliveira, Carlapt_PT
dc.contributor.authorSantos, Manuel A. S.pt_PT
dc.date.accessioned2020-03-04T18:16:41Z-
dc.date.available2020-03-04T18:16:41Z-
dc.date.issued2018-
dc.identifier.issn1547-6286pt_PT
dc.identifier.urihttp://hdl.handle.net/10773/27792-
dc.description.abstractDeregulation of tRNAs, aminoacyl-tRNA synthetases and tRNA modifying enzymes are common in cancer, raising the hypothesis that protein synthesis efficiency and accuracy (mistranslation) are compromised in tumors. We show here that human colon tumors and xenograft tumors produced in mice by two epithelial cancer cell lines mistranslate 2- to 4-fold more frequently than normal tissue. To clarify if protein mistranslation plays a role in tumor biology, we expressed mutant Ser-tRNAs that misincorporate Ser-at-Ala (frequent error) and Ser-at-Leu (infrequent error) in NIH3T3 cells and investigated how they responded to the proteome instability generated by the amino acid misincorporations. There was high tolerance to both misreading tRNAs, but the Ser-to-Ala misreading tRNA was a more potent inducer of cell transformation, stimulated angiogenesis and produced faster growing tumors in mice than the Ser-to-Leu misincorporating tRNA. Upregulation of the Akt pathway and the UPR were also observed. Most surprisingly, the relative expression of both misreading tRNAs increased during tumor growth, suggesting that protein mistranslation is advantageous in cancer contexts. These data highlight new features of protein synthesis deregulation in tumor biology.pt_PT
dc.language.isoengpt_PT
dc.publisherTaylor & Francispt_PT
dc.relationPOCI-01-0145-FEDER-007274pt_PT
dc.relationinfo:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBPD%2F86543%2F2012/PTpt_PT
dc.relationSFRH/BD/76417/2011pt_PT
dc.relationinfo:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBPD%2F26611%2F2006/PTpt_PT
dc.relationinfo:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBD%2F91020%2F2012/PTpt_PT
dc.relationinfo:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBPD%2F89764%2F2012/PTpt_PT
dc.relationinfo:eu-repo/grantAgreement/FCT/5876/147343/PTpt_PT
dc.relationPTDC/BEX-BCM/2121/2014pt_PT
dc.relationinfo:eu-repo/grantAgreement/FCT/COMPETE/132983/PTpt_PT
dc.relationNORTE-01-0145-FEDER-000029pt_PT
dc.rightsrestrictedAccesspt_PT
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectCancerpt_PT
dc.subjectTumor growthpt_PT
dc.subjectmRNA mistranslationpt_PT
dc.subjecttRNAspt_PT
dc.subjectUPRpt_PT
dc.subjecttRNA misreadingpt_PT
dc.subjectProtein biosynthesis errorspt_PT
dc.titleCodon misreading tRNAs promote tumor growth in micept_PT
dc.typearticlept_PT
dc.description.versionpublishedpt_PT
dc.peerreviewedyespt_PT
degois.publication.firstPage773pt_PT
degois.publication.issue6pt_PT
degois.publication.lastPage786pt_PT
degois.publication.titleRNA Biologypt_PT
degois.publication.volume15pt_PT
dc.identifier.doi10.1080/15476286.2018.1454244pt_PT
dc.identifier.essn1555-8584pt_PT
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