In vivo SILAC-based Proteomics Reveals Phosphoproteome Changes during Skin Carcinogenesis
Conference Recording Mar 07, 2013
About the Speaker
Sara Zanivan studied biology at the University of Turin and she obtained her PhD at the Institute for Cancer Research and Treatment, Candiolo, Italy. In November 2010 she moved to the Beatson Institute for Cancer Research, Glasgow, UK, as junior Group Leader of the “Vascular Proteomics” group. Her research interests focus on better understanding the complexity of the molecular mechanisms regulating angiogenesis in cancer using quantitative proteomic approach.
Mouse models of cancer are a resource of great potential in cancer research and they have provided important insights into tumour biology. We addressed one of the major challenges in cancer proteomics and performed a functional proteomic study to investigate the stepwise development of tumour in vivo. We applied an advanced proteomic workflow employing high resolution mass spectrometry in combination with the SILAC mouse technology to the well-established DMBA-TPA two-stage mouse model of skin carcinogenesis. We profiled the phosphoproteome of i) normal skin, ii) epidermal hyperplasia, iii) pre-malignant lesion and iv) invasive squamous cell carcinoma. The more than 6,000 proteins and 12,000 phosphorylation sites identified recapitulate general alteration in tumour cells, such as cell proliferation and metabolic switch to anaerobic glycolysis, but also specific for cutaneous carcinoma, such as the loss of keratinocyte differentiation. Additionally, our unbiased overview provides clear evidence that distinct parts of the proteome and phosphoproteome are regulated during the different steps of carcinogenesis and identifies the specific deregulated processes. Beyond providing a novel approach to discover molecules and mechanisms in carcinoma development and the first in depth functional portrait of skin carcinogenesis, we illustrate the relevance of this approach to human and validated some of the stage specific candidates in human tumour tissues.