Sara Zanivan - Tumour Microenvironment and Proteomics

Introduction

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The tumour stroma is composed of many different cell types and extracellular matrix components that work in concert to generate a microenvironment permissive to tumour initiation, progression and formation of metastasis. Cancer associated fibroblasts (CAFs) are the most abundant non-neoplastic cells in solid tumours. They are characterised by their ability to secrete a plethora of factors that modify the tumour microenvironment and affect the behaviour of or communicate with surrounding cells, including endothelial, cancer and immune cells. For this reason, CAFs play a key role in cancer pathology and are considered a promising target for therapy.

Our group is focused on understanding the role of CAFs in invasion in breast and ovarian cancers. In particular, we aim to identify and characterise novel molecular mechanisms through which CAFs create a pro-invasive and pro-angiogenic tumour microenvironment, and explore the possibility of targeting these cells.

To achieve this, our group exploits and develops in vitro and in vivo models that we investigate using a unique combination of cell and molecular biology approaches together with state-of-the-art quantitative mass spectrometry-based proteomics.

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Lab Report

icon Zanivan Lab Report

Key Publications

Patella F, Schug ZT, Persi E, Neilson LJ, Erami Z, Avanzato D, Maione F, Hernandez-Fernaud JR, Mackay G, Zheng L, Reid S, Frezza C, Giraudo E, Fiorio Pla A, Anderson K, Ruppin E, Gottlieb E, Zanivan S. Proteomics-based metabolic modelling reveals that fatty acid oxidation controls endothelial cell permeability. Mol Cell Proteomics, published online 8 Jan 2015, doi: 10.1074/mcp.M114.045575 mcp.M114.045575

van den Biggelaar M, Hernández-Fernaud JR, van den Eshof BL, Neilson LJ, Meijer AB, Mertens K, Zanivan S. Quantitative phosphoproteomics unveils temporal dynamics of thrombin signaling in human endothelial cells. Blood 123: e22-36, 2014 [doi: 10.1182/blood-2013-12-546036]

Zanivan S, Maione F, Hein MY, Hernández-Fernaud JR, Ostasiewicz P, Giraudo E, Mann M. SILAC-based proteomics of human primary endothelial cell morphogenesis unveils tumor angiogenic markers. Mol Cell Proteomics 12: 3599-611, 2013

Zanivan S, Meves A, Behrendt K, Schoof EM, 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. In Vivo SILAC-Based Proteomics Reveals Phosphoproteome Changes during Mouse Skin Carcinogenesis. Cell Rep 3: 552-66, 2013

Biography

Education and qualifications

2006: PhD, Complex Systems Applied to Post Genomic Biology, University of Torino, Italy
2003: Masters in Bioinformatics, University of Torino, Italy
2001: MS in Biology, University of Torino, Italy

Appointments

2010-present: Group Leader, CRUK Beatson Institute
2007-2010: Postdoctoral Fellow with Matthias Mann, Max Planck Institute of Biochemistry, Martinsried, Germany
2002-2006: PhD Student with Guido Serini and Federico Bussolino, Institute for Cancer Research and Treatment, Torino, Italy

Recent Publications

2017

Reid SE, Kay EJ, Neilson LJ, Henze AT, Serneels J, McGhee EJ, Dhayade S, Nixon C, Mackey JB, Santi A, Swaminathan K, Athineos D, Papalazarou V, Patella F, Román-Fernández Á, ElMaghloob Y, Hernandez-Fernaud JR, Adams RH, Ismail S, Bryant DM, Salmeron-Sanchez M, Machesky LM, Carlin LM, Blyth K, Mazzone M, Zanivan S.Tumor matrix stiffness promotes metastatic cancer cell interaction with the endothelium. EMBO J EMBO J 36: 2373-89, 2017

van den Eshof BL, Hoogendijk AJ, Simpson PJ, van Alphen FPJ, Zanivan S, Mertens K, Meijer AB, van den Biggelaar M (2017) Paradigm of Biased PAR1 (Protease-Activated Receptor-1) Activation and Inhibition in Endothelial Cells Dissected by Phosphoproteomics. Arterioscler Thromb Vasc Biol, in press

Diaz-Vera J, Palmer S, Hernandez-Fernaud JR, Dornier E, Mitchell LE, Macpherson I, Edwards J, Zanivan S, Norman JC. A proteomic approach to identify endosomal cargoes controlling cancer invasiveness. J Cell Sci 130: 697-711, 2017

Hernandez-Fernaud J, Ruengeler E, Casazza A, Neilson L, Pulleine E, Santi A, Ismail S, Lilla S, Dhayade S, Macpherson I, McNeish I, Ennis D, Ali H, Kugeratski F, Al Khamici H, van den Biggelaar M, van den Berghe P, Cloix C, McDonald L, Millan D, Hoyle A, Kuchnio A, Carmeliet P, Valenzuela S, Blyth K, Yin H, Mazzone M, Norman J, Zanivan S. Secreted CLIC3 drives cancer progression through its glutathione-dependent oxidoreductase activity. Nat Commun 8: 14206, 2017

2016

Patella F, Neilson LJ, Athineos D, Erami Z, Anderson KI, Blyth K, Ryan KM, Zanivan S. In-Depth Proteomics Identifies a Role for Autophagy in Controlling Reactive Oxygen Species Mediated Endothelial Permeability. J Proteome Res 15: 2187-97, 2016

Clarke CJ, Berg TJ, Birch J, Ennis D, Mitchell L, Cloix C, Campbell A, Sumpton D, Nixon C, Campbell K, Bridgeman VL, Vermeulen PB, Foo S, Kostaras E, Jones JL, Haywood L, Pulleine E, Yin HB, Strathdee D, Sansom O, Blyth K, McNeish I, Zanivan S, Reynolds AR, Norman JC. The Initiator Methionine tRNA Drives Secretion of Type II Collagen from Stromal Fibroblasts to Promote Tumor Growth and Angiogenesis. Curr Biol 26: 755-65, 2016

2015

Patella F, Schug ZT, Persi E, Neilson LJ, Erami Z, Avanzato D, Maione F, Hernandez-Fernaud JR, Mackay G, Zheng L, Reid S, Frezza C, Giraudo E, Fiorio Pla A, Anderson K, Ruppin E, Gottlieb E, Zanivan S. Proteomics-based metabolic modelling reveals that fatty acid oxidation controls endothelial cell permeability. Mol Cell Proteomics 14: 621-34, 2015

2014

Guo Z, Neilson LJ, Zhong H, Murray PS, Zanivan S, Zaidel-Bar R. E-cadherin interactome complexity and robustness resolved by quantitative proteomics. Sci Signal 7: rs7, 2014

Reid S, Hernandez-Fernaud JR, Zanivan S. In vivo quantitative proteomics for the study of oncometabolism. Methods Enzymol 543: 235-59, 2014

van den Biggelaar M, Hernández-Fernaud JR, van den Eshof BL, Neilson LJ, Meijer AB, Mertens K, Zanivan S. Quantitative phosphoproteomics unveils temporal dynamics of thrombin signaling in human endothelial cells. Blood 123: e22-36, 2014

2013

Zanivan S, Meves A, Behrendt K, Schoof EM, 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. In Vivo SILAC-Based Proteomics Reveals Phosphoproteome Changes during Mouse Skin Carcinogenesis. Cell Rep 3: 552-66, 2013

Zanivan S, Maione F, Hein MY, Hernández-Fernaud JR, Ostasiewicz P, Giraudo E, Mann M. SILAC-based proteomics of human primary endothelial cell morphogenesis unveils tumor angiogenic markers. Mol Cell Proteomics 12: 3599-611, 2013

Neuhauser N, Nagaraj NN, McHardy P, Zanivan S, Scheltema R, Cox J, Mann M. High performance computational analysis of large-scale proteome datasets to assess incremental contribution to coverage of human genome. J Proteome Res. doi: 10.1021/pr400181q, published online 23 Apr 2013

Schiller HB, Hermann MR, Polleux J, Vignaud T, Zanivan S, Friedel CC, Sun Z, Raducanu A, Gottschalk K, Théry M, Mann M and Fässler R. β1- and αv-class integrins cooperate to regulate myosin-II during rigidity sensing of fibronectin-based microenvironments. Nature Cell Biology, in press 2013

2012

Hernandez-Fernaud JR, Reid SE, Neilson LJ, Zanivan S. Quantitative mass spectrometry-based proteomics in angiogenesis. Proteomics Clin Appl doi: 10.1002/prca.201200055, published online 17 Nov 2012

Zanivan S, Krüger M, Mann M. In Vivo Quantitative Proteomics: The SILAC Mouse. Methods Mol Biol 757: 435-50, 2012

Azimifar SB, Bottcher RT, Zanivan S, Grashoff C, Kruger M, Legate KR, Mann M, Fassler R. Induction of membrane circular dorsal ruffles requires co-signalling of integrin-ILK-complex and EGF receptor. J Cell Sci 125: 435-48, 2012

Muller PA, Trinidad AG, Timpson P, Morton JP, Zanivan S, van den Berghe PV, Nixon C, Karim SA, Caswell PT, Noll JE, Coffill CR, Lane DP, Sansom OJ, Neilsen PM, Norman JC, Vousden KH. Mutant p53 enhances MET trafficking and signalling to drive cell scattering and invasion. Oncogene 32(10): 1252-65, 2012

Lab Members

zanivan group

Post-doc

Alice Santi

Scientific Officer

Lisa Neilson

PhD Students

Emily Kay
Fernanda Kugeratski

Former Lab Members

Maartje van den Biggelaar (Scientist, Sanquin Research, Amsterdam, NL)
Francesca Patella (Post-doc, University College London, UK)
Juan Ramon Hernandez (Manager Proteomic Facility, University of Warwick, UK)

Research

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Read more about the Research Groups working at the Beatson Institute.

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Seminars

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Find out more about our seminars including our Distinguished Seminar Programme.

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