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The X-Linked DDX3X ...
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Phung, BengtLund University,Lunds universitet,Melanoma Genomics,Forskargrupper vid Lunds universitet,Lund University Research Groups
(author)
The X-Linked DDX3X RNA Helicase Dictates Translation Reprogramming and Metastasis in Melanoma
- Article/chapterEnglish2019
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Numbers
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LIBRIS-ID:oai:lup.lub.lu.se:45ba3238-adab-4e6a-b5e3-2203dd89306a
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https://lup.lub.lu.se/record/45ba3238-adab-4e6a-b5e3-2203dd89306aURI
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https://doi.org/10.1016/j.celrep.2019.05.069DOI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:art swepub-publicationtype
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Subject category:ref swepub-contenttype
Notes
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The X-linked DDX3X gene encodes an ATP-dependent DEAD-box RNA helicase frequently altered in various human cancers, including melanomas. Despite its important roles in translation and splicing, how DDX3X dysfunction specifically rewires gene expression in melanoma remains completely unknown. Here, we uncover a DDX3X-driven post-transcriptional program that dictates melanoma phenotype and poor disease prognosis. Through an unbiased analysis of translating ribosomes, we identified the microphthalmia-associated transcription factor, MITF, as a key DDX3X translational target that directs a proliferative-to-metastatic phenotypic switch in melanoma cells. Mechanistically, DDX3X controls MITF mRNA translation via an internal ribosome entry site (IRES) embedded within the 5' UTR. Through this exquisite translation-based regulatory mechanism, DDX3X steers MITF protein levels dictating melanoma metastatic potential in vivo and response to targeted therapy. Together, these findings unravel a post-transcriptional layer of gene regulation that may provide a unique therapeutic vulnerability in aggressive male melanomas.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Cieśla, MaciejLund University,Lunds universitet,RNA och stamcellsbiologi,Forskargrupper vid Lunds universitet,RNA and Stem Cell Biology,Lund University Research Groups(Swepub:lu)med-mc1
(author)
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Sanna, AdrianaLund University,Lunds universitet,Melanoma Genomics,Forskargrupper vid Lunds universitet,Lund University Research Groups(Swepub:lu)ad2607sa
(author)
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Guzzi, NicolaLund University,Lunds universitet,RNA och stamcellsbiologi,Forskargrupper vid Lunds universitet,RNA and Stem Cell Biology,Lund University Research Groups(Swepub:lu)med-ngz
(author)
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Beneventi, GiuliaLund University,Lunds universitet,RNA och stamcellsbiologi,Forskargrupper vid Lunds universitet,RNA and Stem Cell Biology,Lund University Research Groups(Swepub:lu)med-gbv
(author)
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Cao Thi Ngoc, PhuongLund University,Lunds universitet,RNA och stamcellsbiologi,Forskargrupper vid Lunds universitet,RNA and Stem Cell Biology,Lund University Research Groups(Swepub:lu)ph4774ca
(author)
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Lauss, MartinLund University,Lunds universitet,Melanoma Genomics,Forskargrupper vid Lunds universitet,Lund University Research Groups(Swepub:lu)med-mlu
(author)
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Cabrita, RitaLund University,Lunds universitet,Melanoma Genomics,Forskargrupper vid Lunds universitet,Lund University Research Groups(Swepub:lu)ri3686ca
(author)
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Cordero, EugeniaLund University,Lunds universitet,Experimentell onkologi,Forskargrupper vid Lunds universitet,Experimental oncology,Lund University Research Groups(Swepub:lu)med-euc
(author)
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Bosch, AnaLund University,Lunds universitet,Molekylära behandlingsstrategier vid bröstcancer,Forskargrupper vid Lunds universitet,Molecular therapeutics in breast cancer,Lund University Research Groups(Swepub:lu)med-abp
(author)
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Rosengren, FridaLund University,Lunds universitet,Melanoma Genomics,Forskargrupper vid Lunds universitet,Lund University Research Groups(Swepub:lu)med-frs
(author)
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Häkkinen, JariLund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)thep-jha
(author)
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Griewank, KlausUniversity Hospital Essen
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Paschen, AnnetteUniversity Hospital Essen
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Harbst, KatjaLund University,Lunds universitet,Melanoma Genomics,Forskargrupper vid Lunds universitet,Lund University Research Groups(Swepub:lu)med-kbn
(author)
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Olsson, HåkanLund University,Lunds universitet,Lunds Melanomstudiegrupp,Forskargrupper vid Lunds universitet,Lund Melanoma Study Group,Lund University Research Groups(Swepub:lu)onk-hol
(author)
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Ingvar, ChristianLund University,Lunds universitet,Kirurgi, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Lunds Melanomstudiegrupp,Forskargrupper vid Lunds universitet,Surgery (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund Melanoma Study Group,Lund University Research Groups,Skåne University Hospital(Swepub:lu)kir-cin
(author)
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Carneiro, AnaLund University,Lunds universitet,Lunds Melanomstudiegrupp,Forskargrupper vid Lunds universitet,Lund Melanoma Study Group,Lund University Research Groups,Skåne University Hospital(Swepub:lu)med-ace
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Tsao, HensinHarvard University
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Schadendorf, DirkUniversity Hospital Essen
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Pietras, KristianLund University,Lunds universitet,Experimentell onkologi,Forskargrupper vid Lunds universitet,Experimental oncology,Lund University Research Groups(Swepub:lu)med-kpi
(author)
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Bellodi, CristianLund University,Lunds universitet,RNA och stamcellsbiologi,Forskargrupper vid Lunds universitet,RNA and Stem Cell Biology,Lund University Research Groups(Swepub:lu)med-cnb
(author)
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Jönsson, GöranLund University,Lunds universitet,Lunds Melanomstudiegrupp,Forskargrupper vid Lunds universitet,Lund Melanoma Study Group,Lund University Research Groups(Swepub:lu)onk-gjo
(author)
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Melanoma GenomicsForskargrupper vid Lunds universitet
(creator_code:org_t)
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In:Cell Reports: Elsevier BV27:12, s. 7-35862211-1247
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- By the author/editor
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Phung, Bengt
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Cieśla, Maciej
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Sanna, Adriana
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Guzzi, Nicola
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Beneventi, Giuli ...
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Cao Thi Ngoc, Ph ...
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show more...
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Lauss, Martin
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Cabrita, Rita
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Cordero, Eugenia
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Bosch, Ana
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Rosengren, Frida
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Häkkinen, Jari
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Griewank, Klaus
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Paschen, Annette
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Harbst, Katja
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Olsson, Håkan
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Ingvar, Christia ...
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Carneiro, Ana
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Tsao, Hensin
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Schadendorf, Dir ...
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Pietras, Kristia ...
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Bellodi, Cristia ...
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Jönsson, Göran
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