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The X-Linked DDX3X ...
The X-Linked DDX3X RNA Helicase Dictates Translation Reprogramming and Metastasis in Melanoma
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- Phung, Bengt (author)
- Lund University,Lunds universitet,Melanoma Genomics,Forskargrupper vid Lunds universitet,Lund University Research Groups
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- Cieśla, Maciej (author)
- Lund University,Lunds universitet,RNA och stamcellsbiologi,Forskargrupper vid Lunds universitet,RNA and Stem Cell Biology,Lund University Research Groups
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- Sanna, Adriana (author)
- Lund University,Lunds universitet,Melanoma Genomics,Forskargrupper vid Lunds universitet,Lund University Research Groups
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- Guzzi, Nicola (author)
- Lund University,Lunds universitet,RNA och stamcellsbiologi,Forskargrupper vid Lunds universitet,RNA and Stem Cell Biology,Lund University Research Groups
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- Beneventi, Giulia (author)
- Lund University,Lunds universitet,RNA och stamcellsbiologi,Forskargrupper vid Lunds universitet,RNA and Stem Cell Biology,Lund University Research Groups
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- Cao Thi Ngoc, Phuong (author)
- Lund University,Lunds universitet,RNA och stamcellsbiologi,Forskargrupper vid Lunds universitet,RNA and Stem Cell Biology,Lund University Research Groups
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- Lauss, Martin (author)
- Lund University,Lunds universitet,Melanoma Genomics,Forskargrupper vid Lunds universitet,Lund University Research Groups
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- Cabrita, Rita (author)
- Lund University,Lunds universitet,Melanoma Genomics,Forskargrupper vid Lunds universitet,Lund University Research Groups
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- Cordero, Eugenia (author)
- Lund University,Lunds universitet,Experimentell onkologi,Forskargrupper vid Lunds universitet,Experimental oncology,Lund University Research Groups
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- Bosch, Ana (author)
- Lund University,Lunds universitet,Molekylära behandlingsstrategier vid bröstcancer,Forskargrupper vid Lunds universitet,Molecular therapeutics in breast cancer,Lund University Research Groups
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- Rosengren, Frida (author)
- Lund University,Lunds universitet,Melanoma Genomics,Forskargrupper vid Lunds universitet,Lund University Research Groups
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- Häkkinen, Jari (author)
- Lund 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
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- Griewank, Klaus (author)
- University Hospital Essen
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- Paschen, Annette (author)
- University Hospital Essen
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- Harbst, Katja (author)
- Lund University,Lunds universitet,Melanoma Genomics,Forskargrupper vid Lunds universitet,Lund University Research Groups
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- Olsson, Håkan (author)
- Lund University,Lunds universitet,Lunds Melanomstudiegrupp,Forskargrupper vid Lunds universitet,Lund Melanoma Study Group,Lund University Research Groups
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- Ingvar, Christian (author)
- Lund 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
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- Carneiro, Ana (author)
- Lund University,Lunds universitet,Lunds Melanomstudiegrupp,Forskargrupper vid Lunds universitet,Lund Melanoma Study Group,Lund University Research Groups,Skåne University Hospital
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- Tsao, Hensin (author)
- Harvard University
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- Schadendorf, Dirk (author)
- University Hospital Essen
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- Pietras, Kristian (author)
- Lund University,Lunds universitet,Experimentell onkologi,Forskargrupper vid Lunds universitet,Experimental oncology,Lund University Research Groups
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- Bellodi, Cristian (author)
- Lund University,Lunds universitet,RNA och stamcellsbiologi,Forskargrupper vid Lunds universitet,RNA and Stem Cell Biology,Lund University Research Groups
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- Jönsson, Göran (author)
- Lund University,Lunds universitet,Lunds Melanomstudiegrupp,Forskargrupper vid Lunds universitet,Lund Melanoma Study Group,Lund University Research Groups
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(creator_code:org_t)
- Elsevier BV, 2019
- 2019
- English.
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In: Cell Reports. - : Elsevier BV. - 2211-1247. ; 27:12, s. 7-3586
- Related links:
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Abstract
Subject headings
Close
- 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
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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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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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
- Articles in the publication
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Cell Reports
- By the university
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Lund University