title: In vivo SILAC-based proteomics reveals phosphoproteome changes during mouse skin carcinogenesis.
abstract: 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.
authors: Department of Proteomics and Signal Transduction, Max-Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany. s.zanivan@beatson.gla.ac.uk
authors: Sara
authors: S
authors: Zanivan
authors: Alexander
authors: A
authors: Meves
authors: Kristina
authors: K
authors: Behrendt
authors: Erwin M
authors: EM
authors: Schoof
authors: Lisa J
authors: LJ
authors: Neilson
authors: Jürgen
authors: J
authors: Cox
authors: Hao R
authors: HR
authors: Tang
authors: Gabriela
authors: G
authors: Kalna
authors: Janine H
authors: JH
authors: van Ree
authors: Jan M
authors: JM
authors: van Deursen
authors: Carol S
authors: CS
authors: Trempus
authors: Laura M
authors: LM
authors: Machesky
authors: Rune
authors: R
authors: Linding
authors: Sara A
authors: SA
authors: Wickström
authors: Reinhard
authors: R
authors: Fässler
authors: Matthias
authors: M
authors: Mann
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement; D002471:Cell Transformation, Neoplastic; D002851:Chromatography, High Pressure Liquid; D015536:Down-Regulation; D006801:Humans; D007553:Isotope Labeling; D051379:Mice; D010212:Papilloma / Q000378:metabolism / Q000473:pathology; D010748:Phosphopeptides / Q000032:analysis / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D020543:Proteome / Q000378:metabolism; D040901:Proteomics; D012867:Skin / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D053719:Tandem Mass Spectrometry; D014025:Titanium / Q000737:chemistry; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D054462:p21-Activated Kinases / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D010748:Phosphopeptides; D020543:Proteome; C009495:titanium dioxide; D014025:Titanium; D019061:src-Family Kinases; D054462:p21-Activated Kinases; D011493:Protein Kinase C