Project description
Role of nicotinic acetylcholine receptors in the development of prostate and colon cancers
Nicotinic acetylcholine receptors (nAChRs) belong to the family of transmembrane ligand-gated ion channels. Tobacco smoking is linked to several types of cancer and tobacco-derived nitrosamines activate nAChRs, contributing to oncogenesis. Recent preliminary data show the clear difference in expression of nAChR subunits between cancerous and non-cancerous cells, obtained from prostate and colon cancer samples. The EU-funded nAChRs-CRC-PCa-IF-RI project will investigate the pathophysiological role of nAChRs in prostate and colorectal cancer. The project objectives are to identify nAChRs involved in prostate and colon cancer, characterise nAChRs’ role in migration, proliferation and invasion, and explore the effects of dupα7, an nAChR subunit, in anti-angiogenesis. The team will also study the influence of chemotherapy on nAChRs’ expression.
Objective
Nicotinic acetylcholine receptors (nAChRs) are transmembrane ligand gated ion channels composed of five subunits and encoded by 16 genes. Depending on the subunit composition nAChRs have different properties and functions. It is widely accepted that smoking tobacco is correlated with several types of cancers and that nicotine and tobacco-derived nitrosamines are known to activate nAChRs contributing to oncogenic processes. To date the question of whether nAChRs contribute to the cellular malfunctions involved in prostate and colon cancer still remains unanswered. Our preliminary results show for the first-time different expression levels of nAChRs subunits in prostate and colon cancer cell lines. Most strikingly is the clear difference of expression of nAChRs subunits between cancerous vs. non-cancerous cells, depending on the aggressiveness and cell type. The question arises whether these differences have a physiological impact. In the present project I will investigate the pathophysiological role of nAChRs in prostate and colorectal cancer. My aim is to (1) Identify and characterize nAChRs involved in prostate and colon cancer; (2) study the role of nAChRs in migration, proliferation and invasion in prostate and colon cancer; (3) the influence of a duplicated isoform of the α7 nAChR subunit, dupα7, and its anti-angiogenic properties in CRC and PCa; and (4) the role of chemotherapeutic drugs, which could augment nAChRs expression in cancer and contribute to chemoresistance. The present project will be performed at the laboratory of Dr. Peinelt University of Bern, an established research group with a focus on the pathophysiology of ion channels in prostate and colorectal cancer and in collaboration with the Urology Department of the University Hospital Inselspital Bern. The Marie Curie IF will help me to further develop leadership skills, scientific maturity and independence and will be crucial for my aim to obtain an independent academic position in the future.
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Funding Scheme
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinator
3012 Bern
Switzerland