Sigma-1 Receptor Biology

Tumour Biology and Metastasis Team

Section: Cancer Research UK Cancer Therapeutics Unit

The sigma-1 receptor is an internal membrane protein which is overexpressed in many cancers and has been used for clinical diagnosis and imaging. It may also serve as a target for therapy since it provides anti-apoptotic signals during tumour cell proliferation and the invasion of normal physiological boundaries. However, the underlying molecular mechanisms remain elusive. The sigma 1 receptor has been cloned and recombinant protein expressed. Peptides generated from two different regions of the protein have been used to raise monoclonal antibodies for localisation and functional studies. Green fluorescent protein (GFP) fusion proteins have also been generated and used for FRET (Fluorescence Resonance Energy Transfer) and FCCM (Fluorescence Cross-Correlation Microscopy) to investigate interactions between the sigma receptor and putative molecular partners.

We have shown that it is localised on the ER membrane where it co-localises with the IP3 receptor and PLCγ. The aim is to clarify the signalling pathways linked to this receptor and to shed light on the differential sensitivity of tumour cells (and activated endothelial cells) to apoptosis induction by specific synthetic sigma ligands.