MTSS1 is a metastasis driver in a subset of human melanomas

Nat Commun. 2014 Mar 17;5:3465. doi: 10.1038/ncomms4465.

Abstract

In cancers with a highly altered genome, distinct genetic alterations drive subsets rather than the majority of individual tumours. Here we use a sequential search across human tumour samples for transcript outlier data points with associated gene copy number variations that correlate with patient's survival to identify genes with pro-invasive functionality. Employing loss and gain of function approaches in vitro and in vivo, we show that one such gene, MTSS1, promotes the ability of melanocytic cells to metastasize and engages actin dynamics via Rho-GTPases and cofilin in this process. Indeed, high MTSS1 expression defines a subgroup of primary melanomas with unfavourable prognosis. These data underscore the biological, clinical and potential therapeutic implications of molecular subsets within genetically complex cancers.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Melanoma / genetics
  • Melanoma / metabolism*
  • Melanoma / pathology
  • Mice, Nude
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism*
  • Neoplasm Metastasis*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*

Substances

  • MTSS1 protein, human
  • Microfilament Proteins
  • Neoplasm Proteins