The X-Linked DDX3X RNA Helicase Dictates Translation Reprogramming and Metastasis in Melanoma

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift


title = "The X-Linked DDX3X RNA Helicase Dictates Translation Reprogramming and Metastasis in Melanoma",
abstract = "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.",
author = "Bengt Phung and Maciej Cieśla and Adriana Sanna and Nicola Guzzi and Giulia Beneventi and {Cao Thi Ngoc}, Phuong and Martin Lauss and Rita Cabrita and Eugenia Cordero and Ana Bosch and Frida Rosengren and Jari H{\"a}kkinen and Klaus Griewank and Annette Paschen and Katja Harbst and H{\aa}kan Olsson and Christian Ingvar and Ana Carneiro and Hensin Tsao and Dirk Schadendorf and Kristian Pietras and Cristian Bellodi and G{\"o}ran J{\"o}nsson",
note = "Copyright {\circledC} 2019 The Author(s). Published by Elsevier Inc. All rights reserved.",
year = "2019",
month = "6",
day = "18",
doi = "10.1016/j.celrep.2019.05.069",
language = "English",
volume = "27",
pages = "3573--3586.e7",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "12",