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Melanoma addiction to the long non-coding RNA SAMMSON

(2016) NATURE. 531(7595). p.518-522
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Abstract
Focal amplifications of chromosome 3p13-3p14 occur in about 10% of melanomas and are associated with a poor prognosis. The melanoma-specific oncogene MITF resides at the epicentre of this amplicon(1). However, whether other loci present in this amplicon also contribute to melanomagenesis is unknown. Here we show that the recently annotated long non-coding RNA (lncRNA) gene SAMMSON is consistently co-gained with MITF. In addition, SAMMSON is a target of the lineage-specific transcription factor SOX10 and its expression is detectable in more than 90% of human melanomas. Whereas exogenous SAMMSON increases the clonogenic potential in trans, SAMMSON knockdown drastically decreases the viability of melanoma cells irrespective of their transcriptional cell state and BRAF, NRAS or TP53 mutational status. Moreover, SAMMSON targeting sensitizes melanoma to MAPK-targeting therapeutics both in vitro and in patient-derived xenograft models. Mechanistically, SAMMSON interacts with p32, a master regulator of mitochondrial homeostasis and metabolism, to increase its mitochondrial targeting and pro-oncogenic function. Our results indicate that silencing of the lineage addiction oncogene SAMMSON disrupts vital mitochondrial functions in a cancer-cell-specific manner; this silencing is therefore expected to deliver highly effective and tissue-restricted anti-melanoma therapeutic responses.
Keywords
TARGET, SURVIVAL, P32/GC1QR, MITOCHONDRIAL TRANSLATION, P-32 PROTEIN, OXIDATIVE-PHOSPHORYLATION, METABOLISM, PROLIFERATION, MORPHOLOGY, PGC1-ALPHA

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Chicago
Leucci, Eleonora, Roberto Vendramin, Marco Spinazzi, Patrick Laurette, Mark Fiers, Jasper Wouters, Enrico Radaelli, et al. 2016. “Melanoma Addiction to the Long Non-coding RNA SAMMSON.” Nature 531 (7595): 518–522.
APA
Leucci, E., Vendramin, R., Spinazzi, M., Laurette, P., Fiers, M., Wouters, J., Radaelli, E., et al. (2016). Melanoma addiction to the long non-coding RNA SAMMSON. NATURE, 531(7595), 518–522.
Vancouver
1.
Leucci E, Vendramin R, Spinazzi M, Laurette P, Fiers M, Wouters J, et al. Melanoma addiction to the long non-coding RNA SAMMSON. NATURE. 2016;531(7595):518–22.
MLA
Leucci, Eleonora, Roberto Vendramin, Marco Spinazzi, et al. “Melanoma Addiction to the Long Non-coding RNA SAMMSON.” NATURE 531.7595 (2016): 518–522. Print.
@article{7222564,
  abstract     = {Focal amplifications of chromosome 3p13-3p14 occur in about 10\% of melanomas and are associated with a poor prognosis. The melanoma-specific oncogene MITF resides at the epicentre of this amplicon(1). However, whether other loci present in this amplicon also contribute to melanomagenesis is unknown. Here we show that the recently annotated long non-coding RNA (lncRNA) gene SAMMSON is consistently co-gained with MITF. In addition, SAMMSON is a target of the lineage-specific transcription factor SOX10 and its expression is detectable in more than 90\% of human melanomas. Whereas exogenous SAMMSON increases the clonogenic potential in trans, SAMMSON knockdown drastically decreases the viability of melanoma cells irrespective of their transcriptional cell state and BRAF, NRAS or TP53 mutational status. Moreover, SAMMSON targeting sensitizes melanoma to MAPK-targeting therapeutics both in vitro and in patient-derived xenograft models. Mechanistically, SAMMSON interacts with p32, a master regulator of mitochondrial homeostasis and metabolism, to increase its mitochondrial targeting and pro-oncogenic function. Our results indicate that silencing of the lineage addiction oncogene SAMMSON disrupts vital mitochondrial functions in a cancer-cell-specific manner; this silencing is therefore expected to deliver highly effective and tissue-restricted anti-melanoma therapeutic responses.},
  author       = {Leucci, Eleonora and Vendramin, Roberto and Spinazzi, Marco and Laurette, Patrick and Fiers, Mark and Wouters, Jasper and Radaelli, Enrico and Eyckerman, Sven and Leonelli, Carina and Vanderheyden, Katrien and Rogiers, Aljosja and Hermans, Els and Baatsen, Pieter and Aerts, Stein and Amant, Frederic and Van Aelst, Stefan and van den Oord, Joost and de Strooper, Bart and Davidson, Irwin and Lafontaine, Denis LJ and Gevaert, Kris and Vandesompele, Jo and Mestdagh, Pieter and Marine, Jean-Christophe},
  issn         = {0028-0836},
  journal      = {NATURE},
  language     = {eng},
  number       = {7595},
  pages        = {518--522},
  title        = {Melanoma addiction to the long non-coding RNA SAMMSON},
  url          = {http://dx.doi.org/10.1038/nature17161},
  volume       = {531},
  year         = {2016},
}

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