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Merkel cell polyomavirus Oncogenic Network

Merkel cell polyomavirus Oncogenic Network

Objective

The aim of the MONET project (Merkel cell polyomavirus Oncogenic Network) is to provide a state-of-the-art understanding of Merkel cell carcinoma (MCC) tumorigenesis. Viral pathogens are estimated to be responsible of ~12% of cancers worldwide and represent useful models for the study of oncogenesis mechanisms. Merkel Cell Carcinoma (MCC) is an aggressive neuroendocrine skin cancer detected in ~2500 patients per year in Europe and has recently been linked with a clonal integration of the Merkel Cell polyomavirus (MCPyV) in more than 80% of cases. MCPyV is a 6-protein encoding system, expressing only two proteins with reported oncogenic functions. This limited proteome size thus allows system-wide study of its associated oncogenic mechanisms. This multi-pronged project consists of: (i) identifying the critical interactions of viral and host proteins in MCC oncogenesis; and (ii), using NOD scid mice cell line derived xenografts (CDXs), validate MCPyV host-proteins drug targeting strategies to combat MCC tumorigenesis. Using cutting-edge mass spectrometry-based techniques combined with CRISPR interference approaches in relevant human cancer cell systems, these studies will uncover new protein-protein interactions essential for tumorigenesis. MCPyV+ MCC CDXs will be used to establish the functional relevance of novel virus-host protein interactions and to assess the therapeutic potential of targeting these host interactors as anti-cancer strategies. The application of these proteomic and functional approaches will allow for a better understanding of MCPyV-associated carcinogenesis. In a broader view, it will define a new framework for identifying druggable targets in pathogen-driven cancers. This project will underpin future translational researches, and hence appears as a fundamental step for therapeutic development.
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Coordinator

UNIVERSITE DE LILLE

Address

42 Rue Paul Duez
59800 Lille

France

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 196 707,84

Project information

Grant agreement ID: 843052

Status

Grant agreement signed

  • Start date

    2 September 2019

  • End date

    1 September 2021

Funded under:

H2020-EU.1.3.2.

  • Overall budget:

    € 196 707,84

  • EU contribution

    € 196 707,84

Coordinated by:

UNIVERSITE DE LILLE

France