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ECM and TFEB interplay: from building multidisciplinary devices to unravelling the missing link in cancer

Project description

Unraveling the role of the extracellular matrix in tumourigenesis

Accumulating evidence underscores the importance of the surrounding tumour microenvironment or niche in tumour development and growth. Recreating this complex tumour niche in the lab has proven challenging due to the intricate physical and biochemical properties of the extracellular matrix (ECM) and the limitations of available biomimetic materials. Funded by the Marie Skłodowska-Curie Actions programme, the ETICAN project focuses on the ECM and its role in bladder cancer. Researchers will generate a tailored microenvironment in vitro for bladder cancer and investigate the properties of the ECM and its interaction with cancer cells. Moreover, the project aims to identify new drug targets and improve cancer therapy.

Objective

Over the last 30 years, researchers have shown that tumor cells not only need to accumulate oncogenic genetic alterations, but also rely on permissive cues from a surrounding extracellular matrix (ECM) for malignant progression. However, reconstructing the tumor niche in vitro has not been easy due to the complexity of its intertwined physico- biochemical properties and the limitation of the available biomimetic scaffolds. Furthermore, preclinical studies have mainly focused on druggable targets at the intracellular signaling level and overlooked the implication of the ECM. To overcome these hurdles, we will unravel the ECM mechano-chemical contribution in tumorigenesis and its continuum interaction with tumor cells in 3 steps. First, we will deconstruct bladder cancer ECM through in-depth analysis of its physical and biochemical features. This will provide us a blueprint to follow, in order to build a tailored microenvironment for bladder tumoroids. Then, we will reassemble ECM properties in a new generation of tunable materials, functionalized with ECM proteins secreted by bladder cancer cells in vitro. Using our developed tumoroid model, we will finally chart the reciprocal crosstalk between extracellular cues and transcription factor EB (TFEB), an emerging oncogene and regulator of tumor microenvironment. By bridging the gap between ECM and TFEB regulation, we anticipate to catalyse the success of cancer prevention and therapy leveraging new druggable targets at the level of the reciprocal feedback between the evolving ECM and tumor cells.

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2022-PF-01

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Coordinator

INSTITUT GUSTAVE ROUSSY
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 195 914,88
Address
Rue Camille Desmoulins 39
94805 Villejuif
France

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Region
Ile-de-France Ile-de-France Val-de-Marne
Activity type
Research Organisations
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Total cost

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