MetaTarGet · Targeting metabolic regulation in metastasis formation
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2019-07-18 → 2021-07-17
- EU contribution
- €166,320
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
Lines connect the coordinator with its partners.
Results in brief
Targeting metabolic regulation in metastasis formation
Metastasis is the process by which breast cancer cells leave the breast and begin to grow and divide in another part of the body, such as the lung. This process causes more than 90% of breast cancer-related death worldwide. This is mainly because cancer patients often only request medical assistance once cancer cells are already disseminated to other organs. Therefore, there is an urgent need for a better understanding of metastatic disease in order to identify new treatments. Metabolism comprises the chemical reactions that take place within each cell of a living organism and that provide energy for vital processes and for synthesizing new organic material. Metastatic cells regulate their metabolism to be able to colonize the new organ and extract energy and nutrients from this environment to sustain their growth. In this project, I studied how metabolized nutrients are directly used by the tumor cells in two important processes for metastatic disease: the production of extracellular matrix (which provides support and anchorage for the shape of the colonizing cells) and the activation of the NFkB pathway (an important signaling pathway for the process of metastasis). The knowledge gained by studying how breast cancer cells can use available nutrients in foreign organs is expected to stimulate the development of novel therapeutic strategies for preventing and/or treating breast cancer metastasis.
Data: CORDIS, © European Union
Project objective
Distant metastases, i.e. secondary tumors, are the leading cause of cancer deaths. Many patients (especially with breast cancer) are diagnosed when cancer cells have already disseminated to distant organs. Thus, it is of profound importance to prevent the metastatic outgrowth of these disseminated cancer cells into secondary tumors. The ability to remodel the extracellular matrix (ECM) of the metastatic niche is essential for disseminated breast cancer cells to promote their own metastatic outgrowth. This process is to date believed to be transcriptionally regulated. However, the Fendt laboratory has discovered that the nutrient pyruvate metabolically drives ECM remodeling by breast cancer cells. In my project, I will build on this discovery and explore how to target ECM remodeling in metastatic outgrowth. First, I will determine the interaction between the discovered metabolic and the known transcriptional regulation of ECM remodeling. Secondly, I will translate this novel finding into therapeutic potential by defining how to selectively target it, thereby impairing metastatic outgrowth in the lung environment. Thirdly, I will define how the metastatic site and the cancer cell origin affect the discovered metabolic regulation of ECM remodeling, and thus metastatic outgrowth. To address these aims, I will use metabolomics, 13C tracer analysis, genetic engineering and nanotechnology-based drug-delivery in breast cancer 3D cultures and mouse models. With MetaTarGet, I will deliver (i) a mechanistic understanding of pyruvate metabolism as a regulator of ECM remodeling, and (ii) a novel therapeutic strategy to target metastatic outgrowth. This project will allow me to bridge my nanotechnology-based drug-delivery knowledge with the expertise of the Fendt laboratory in metastasis metabolism. Consequently, I will strengthen my research competences and enhance my personal research profile.
Original text from CORDIS.
Participants
- VIB VZW · ZWIJNAARDE - GENTCoordinatorBelgium
Links
Data: CORDIS, © European Union