Sara Sigismund wins a grant of the European Commission to investigate EGF receptor signalling localized in cell microdomains

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ERC consolidator grant is a European funding meant to support researchers with a highly promising scientific track record, who want to consolidate their independence by establishing a research team and continuing to develop a success career in Europe.

Sara Sigismund, researcher of the department of experimental oncology, wins an ERC Consolidator Grant to explore the intracellular signalling occurring in specific microdomains inside the cell in response to epidermal growth factor (EGF) stimulation.

The receptor of epidermal growth factor (EGFR) is expressed on the cell surface of different cell types and plays critical roles in regulating physiological processes such as cell proliferation, survival, differentiation and migration. Altered regulation of EGFR is involved in several pathological conditions, including cancer.

Upon EGF binding, EGFR can be internalized through two alternative routes: clathrin-mediated endocytosis (in which the internalization of molecules expressed on the cell membrane requires the activity of the clathrin protein), stimulated by low EGF concentration, which leads to receptor recycling and re-exposure on the cell membrane –sustaining EGFR-mediated signalling– and non-clathrin endocytosis, stimulated by high EGF concentration, which ends up in receptor degradation and attenuation of EGF-induced signals.

The mechanism of receptor internalization through non-clathrin endocytosis involves the physical interaction of cell membrane –in specific regions where EGFR is located–, mitochondria and endoplasmic reticulum, as well as calcium signals, namely rapid oscillations of calcium concentration localized in those restricted areas.

Thanks to this funding, Sara Sigismund will assess whether these restricted areas, in which cell membrane, mitochondria and endoplasmic reticulum interact and communicate, represent “functional microdomains” of the cell with specific function, organizing and facilitating cellular processes by bringing together the required components: she will analyse in depth the specific related signalling, the effect of such signalling on mitochondria physiology and cell metabolism, and the relevance of this mechanism for cell migration, proliferation and differentiation. These studies will expand the current understanding of EGFR-related signalling, possibly unveiling cell processes not previously associated with EGFR pathway and providing additional tools to modulate such processes in cancer.