Annemiek van Spriel (Dept. Tumor Immunology) has been awarded a prestigious ERC consolidator grant (2.000.000 Euro) to investigate tetraspanin proteins on tumour cells.
Cancer development is characterized by uncontrolled proliferation, cell survival and metabolic reprogramming. Tumour cells are surrounded by a fluid-mosaic membrane that contains tetraspanins which are evolutionary conserved proteins important in the formation of multiprotein complexes at the cell surface (‘Tetraspanin web’). Increasing evidence indicates that Tetraspanins are involved in cancer, still the architecture of the Tetraspanin web in native tumour membranes and its (patho)physiological functions have not been resolved.
Van Spriel’s team recently discovered that the clinical outcome in patients with B cell lymphoma, worldwide the most common haematological malignancy, is directly related to the expression of the Tetraspanin CD37 [de Winde et al. J. Clin. Invest 2016]. In proof-of-concept experiments, defective metabolic signalling was identified in Tetraspanin-deficient tumour cells. The overall aim of the ERC project Secret Surface is to unravel the composition, physiological functions and molecular mechanisms of the Tspan web on tumour development and clinical outcome.
The scientific impact of Secret Surface is an improved understanding of how cell surface receptors and membrane-proximal signalling proteins are organized by the Tetraspanin web in tumour cells, which has far-reaching implications in cell biology and oncology.