Reducing MYC's transcriptional footprint unveils a good prognostic gene signature in melanoma
Open Access
- 1 April 2023
- journal article
- research article
- Published by Cold Spring Harbor Laboratory in Genes & Development
- Vol. 37 (7-8), 303-320
- https://doi.org/10.1101/gad.350078.122
Abstract
MYC's key role in oncogenesis and tumor progression has long been established for most human cancers. In melanoma, its deregulated activity by amplification of 8q24 chromosome or by upstream signaling coming from activating mutations in the RAS/RAF/MAPK pathway—the most predominantly mutated pathway in this disease—turns MYC into not only a driver but also a facilitator of melanoma progression, with documented effects leading to an aggressive clinical course and resistance to targeted therapy. Here, by making use of Omomyc, the most characterized MYC inhibitor to date that has just successfully completed a phase I clinical trial, we show for the first time that MYC inhibition in melanoma induces remarkable transcriptional modulation, resulting in severely compromised tumor growth and a clear abrogation of metastatic capacity independently of the driver mutation. By reducing MYC's transcriptional footprint in melanoma, Omomyc elicits gene expression profiles remarkably similar to those of patients with good prognosis, underlining the therapeutic potential that such an approach could eventually have in the clinic in this dismal disease.Keywords
Funding Information
- Juan de la Cierva programme
- Spanish Ministry of Economy and Competitiveness (IJCI-2014-22403)
- Fundació la Marató de TV3 (474/C/2019)
- Spanish Ministry of Science and Innovation PFIS (FI20/00274)
- Generalitat de Catalunya
- Contractació de Personal Investigador Novell (2016FI_B 00592)
- Spanish Ministry of Science and Innovation (PI19/01277)
- Retos-Colaboración 2019 (RTC2019-007067-1)
- La Marato TV3
- Generalitat de Catalunya AGAUR 2017 (SGR-3193)
- European Research Council (813132)
This publication has 60 references indexed in Scilit:
- Enrichr: interactive and collaborative HTML5 gene list enrichment analysis toolBMC Bioinformatics, 2013
- Inhibition of Myc family proteins eradicates KRas-driven lung cancer in miceGenes & Development, 2013
- Dual Suppression of the Cyclin-Dependent Kinase Inhibitors CDKN2C and CDKN1A in Human MelanomaJNCI Journal of the National Cancer Institute, 2012
- The role of 8q24 copy number gains and c-MYC expression in amelanotic cutaneous melanomaLaboratory Investigation, 2012
- Fiji: an open-source platform for biological-image analysisNature Methods, 2012
- The Action Mechanism of the Myc Inhibitor Termed Omomyc May Give Clues on How to Target Myc for Cancer TherapyPLOS ONE, 2011
- Growth inhibition of SK-MEL-30 human melanoma cells by antisense c-myc oligonucleotides delivered by poly(N-isopropylacrylamide)/ poly(ethyleneimine) copolymerJournal of Tissue Engineering and Regenerative Medicine, 2009
- c-MYC Delays Prometaphase by Direct Transactivation of MAD2 and BubR1: Identification of Mechanisms Underlying c-MYC-Induced DNA Damage and Chromosomal InstabilityCell Cycle, 2007
- Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profilesProceedings of the National Academy of Sciences of the United States of America, 2005
- Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT MethodMethods, 2001