Proinvasion metastasis drivers in early-stage melanoma are oncogenes

Cancer Cell. 2011 Jul 12;20(1):92-103. doi: 10.1016/j.ccr.2011.05.025.


Clinical and genomic evidence suggests that the metastatic potential of a primary tumor may be dictated by prometastatic events that have additional oncogenic capability. To test this "deterministic" hypothesis, we adopted a comparative oncogenomics-guided function-based strategy involving: (1) comparison of global transcriptomes of two genetically engineered mouse models with contrasting metastatic potential, (2) genomic and transcriptomic profiles of human melanoma, (3) functional genetic screen for enhancers of cell invasion, and (4) evidence of expression selection in human melanoma tissues. This integrated effort identified six genes that are potently proinvasive and oncogenic. Furthermore, we show that one such gene, ACP5, confers spontaneous metastasis in vivo, engages a key pathway governing metastasis, and is prognostic in human primary melanomas.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Phosphatase / genetics
  • Acid Phosphatase / metabolism
  • Animals
  • Cell Lineage / genetics
  • Conserved Sequence / genetics
  • Evolution, Molecular
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Genome / genetics
  • Humans
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Kaplan-Meier Estimate
  • Melanoma / genetics*
  • Melanoma / pathology*
  • Mice
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Oncogenes / genetics*
  • Phosphorylation
  • Reproducibility of Results
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / pathology*
  • Tartrate-Resistant Acid Phosphatase
  • Tissue Array Analysis


  • Isoenzymes
  • ACP5 protein, human
  • Acid Phosphatase
  • Acp5 protein, mouse
  • Tartrate-Resistant Acid Phosphatase

Associated data

  • GEO/GSE29074