The role of CD2AP for extracellular vesicle biogenesis

• Applicant: Dr. Kerstin Menck
• Subject Area: Hematology, Oncology ; Cell Biology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 564976539

Extracellular vesicles (EVs) are small (diameter <1μm) membrane particles that are released by all living cells and act as important mediators of intercellular communication. They play a significant role during tumor progression by transporting biomolecules from the tumor cells to the surrounding microenvironment, thus supporting tumor growth and spreading. EVs can either be directly shed from the cell membrane or derive from intracellular compartments in which they are stored until they are released into the extracellular space. Unfortunately, the molecular mechanisms governing the biogenesis of the distinct EV subpopulations are scarcely understood which hampers their use as therapeutic targets. Our data have identified the intracellular adaptor protein CD2AP as a novel regulator of EV secretion. Interestingly, CD2AP seems to be involved in the biogenesis of EVs from the cell membrane as well as from within the cell by regulating their numbers and protein cargo. Moreover, CD2AP has great translational relevance as it is often found overexpressed in breast cancer, in which high expression levels are associated with worse patient survival. In this project, we aim to investigate the molecular mechanisms how CD2AP controls EV budding from the cell membrane as well as the functional consequences for the malignant phenotype of tumor EVs. We will use cell biological and biochemical approaches to reveal the intracellular localization and interaction partners of CD2AP as well as the origin of the CD2AP-induced EV release. In functional assays, we will test the significance of the CD2AP-regulated EVs for the invasiveness, migration and adhesion of breast cancer cells. Taken together, this project will lead to novel insights into the heterogeneity, biogenesis and function of EVs in the context of human cancer.

• DFG Programme: Research Grants