MONET · Merkel cell polyomavirus Oncogenic Network
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2019-09-02 → 2021-09-01
- EU contribution
- €196,708
- Participants
- 2
- Scheme
- MSCA-IF-EF-RI
Lines connect the coordinator with its partners.
Results in brief
Merkel cell polyomavirus Oncogenic Network
The aim of the MONET project is to finely decipher the Merkel Cell polyomavirus (MCPyV) oncogenic mechanisms in Merkel cell carcinoma (MCC). Viral pathogens are estimated to be responsible of ~12% of cancers worldwide, thus deserving extensive investigations and representing useful models for the study of oncogenesis mechanisms. The MCC is an aggressive neuroendocrine skin cancer detected in ~2500 patients per year in Europe. It has recently been linked with a clonal integration of MCPyV in more than 80% of cases. MCPyV is a 6-protein encoding virus, expressing only two proteins with reported oncogenic functions. This minimal transformation system thus allows system-wide study of its associated oncogenic mechanisms. Using cutting-edge mass spectrometry-based techniques in human cancer cell systems, these studies overall objective is to identify new protein-protein interactions essential for tumorigenesis. It aims at underpinning future translational researches, and hence appears as a fundamental step for therapeutic development. It has however been impacted by the COVID-19, as explain further in the next section. Preliminary interactomics results unveil a novel axis potentially involved in MCPyV tumor antigens (TAs)-driven oncogenesis. Mining these proteomic and functional approaches allowed for a better understanding of MCPyV-associated carcinogenesis. In a broader view, it defines 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.
Data: CORDIS, © European Union
Project 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.
Original text from CORDIS.
Participants
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Data: CORDIS, © European Union