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

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; M. Mann

doi:10.1016/j.celrep.2013.01.003

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

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, M. Mann

Novo Nordisk Foundation Center for Protein Research

78 Citations (Scopus)

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.

Original language	English
Journal	Cell Reports
Volume	3
Issue number	2
Pages (from-to)	552-566
Number of pages	15
DOIs	https://doi.org/10.1016/j.celrep.2013.01.003
Publication status	Published - 21 Feb 2013

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Zanivan, S., Meves, A., Behrendt, K., Schoof, E., Neilson, L. J., Cox, J., Tang, H. R., Kalna, G., van Ree, J. H., van Deursen, J. M., Trempus, C. S., Machesky, L. M., Linding, R., Wickström, S. A., Fässler, R., & Mann, M. (2013). In Vivo SILAC-Based Proteomics Reveals Phosphoproteome Changes during Mouse Skin Carcinogenesis. Cell Reports, 3(2), 552-566. https://doi.org/10.1016/j.celrep.2013.01.003

Zanivan, S, Meves, A, Behrendt, K, Schoof, E, Neilson, LJ, Cox, J, Tang, HR, Kalna, G, van Ree, JH, van Deursen, JM, Trempus, CS, Machesky, LM, Linding, R, Wickström, SA, Fässler, R & Mann, M 2013, 'In Vivo SILAC-Based Proteomics Reveals Phosphoproteome Changes during Mouse Skin Carcinogenesis', Cell Reports, vol. 3, no. 2, pp. 552-566. https://doi.org/10.1016/j.celrep.2013.01.003

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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.",

author = "S. Zanivan and A. Meves and K. Behrendt and Erwin Schoof and L.J. Neilson and J. Cox and H.R. Tang and G. Kalna and {van Ree}, J.H. and {van Deursen}, J.M. and C.S. Trempus and L.M. Machesky and Rune Linding and S.A. Wickstr{\"o}m and R. F{\"a}ssler and M. Mann",

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doi = "10.1016/j.celrep.2013.01.003",

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T1 - In Vivo SILAC-Based Proteomics Reveals Phosphoproteome Changes during Mouse Skin Carcinogenesis

AU - Zanivan, S.

AU - Meves, A.

AU - Behrendt, K.

AU - Schoof, Erwin

AU - Neilson, L.J.

AU - Cox, J.

AU - Tang, H.R.

AU - Kalna, G.

AU - van Ree, J.H.

AU - van Deursen, J.M.

AU - Trempus, C.S.

AU - Machesky, L.M.

AU - Linding, Rune

AU - Wickström, S.A.

AU - Fässler, R.

AU - Mann, M.

PY - 2013/2/21

Y1 - 2013/2/21

N2 - 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.

AB - 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.

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

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