Descrizione del progetto
Il ruolo dei recettori nicotinici dell’acetilcolina nello sviluppo dei tumori a prostata e colon
I recettori nicotinici dell’acetilcolina (nAChR, Nicotinic Acetylcholine Receptor) appartengono alla famiglia dei canali ionici transmembrana attivati da ligando. Il tabagismo viene collegato a vari tipi di cancro e le nitrosamine derivate dal tabacco attivano i nAChR, contribuendo all’oncogenesi. Dati preliminari recenti mostrano la netta differenza nell’espressione di subunità nAChR tra cellule tumorali e non, ricavate da campioni di tumori prostatici e del colon. Il progetto nAChRs-CRC-PCa-IF-RI, finanziato dall’UE, studierà il ruolo fisiopatologico dei nAChR nei tumori prostatici e del colon. Gli obiettivi del progetto sono l’identificazione dei nAChR implicati nei tumori a prostata e colon, la caratterizzazione del ruolo dei nAChR nei processi di migrazione, proliferazione e invasione, nonché l’esame degli effetti di dupα7, una subunità dei nAChR, nell’antiangiogenesi. Il team studierà inoltre l’influenza della chemioterapia sull’espressione dei nAChR.
Obiettivo
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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Meccanismo di finanziamento
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinatore
3012 Bern
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