In Vivo SILAC-Based Proteomics Reveals Phosphoproteome Changes during Mouse Skin Carcinogenesis

Research output: Contribution to journalJournal article

  • S. Zanivan
  • A. Meves
  • K. Behrendt
  • Erwin Schoof
  • L.J. Neilson
  • J. Cox
  • H.R. Tang
  • G. Kalna
  • J.H. van Ree
  • J.M. van Deursen
  • C.S. Trempus
  • L.M. Machesky
  • Rune Linding
  • S.A. Wickström
  • R. Fässler
  • Mann, Matthias
Cancer progresses through distinct stages, and mouse models recapitulating traits of this progression are frequently used to explore genetic, morphological, and pharmacological aspects of tumor development. To complement genomic investigations of this process, we here quantify phosphoproteomic changes in skin cancer development using the SILAC mouse technology coupled to high-resolution mass spectrometry. We distill protein expression signatures from our data that distinguish between skin cancer stages. A distinct phosphoproteome of the two stages of cancer progression is identified that correlates with perturbed cell growth and implicates cell adhesion as a major driver of malignancy. Importantly, integrated analysis of phosphoproteomic data and prediction of kinase activity revealed PAK4-PKC/SRC network to be highly deregulated in SCC but not in papilloma. This detailed molecular picture, both at the proteome and phosphoproteome level, will prove useful for the study of mechanisms of tumor progression. SILAC technology in combination with high-resolution mass spectrometry (MS) can be successfully used to measure phosphoproteomes in vivo. Here, Zanivan, Mann, and colleagues have applied SILAC-based MS to investigate phosphoproteomic changes during skin carcinogenesis, using the DMBA/TPA two-stage mouse model. Using this approach, the authors have revealed the phosphoproteomic dynamics that accompany skin cancer progression and predict specific kinase activities associated with tumor malignancy.
Original languageEnglish
JournalCell Reports
Issue number2
Pages (from-to)552-566
Number of pages15
Publication statusPublished - 21 Feb 2013

ID: 46455122