Descripción del proyecto
El papel de los receptores nicotínicos de la acetilcolina en el desarrollo del cáncer de próstata y el cáncer de colon
Los receptores nicotínicos de la acetilcolina (nAchR) pertenecen a la familia de los canales iónicos transmembrana activados por ligando. El tabaquismo está vinculado con varios tipos de cáncer y las nitrosaminas derivadas del tabaco activan nAchR, lo que contribuye a la oncogénesis. Datos preliminares recientes muestran la clara diferencia en la expresión de subunidades de nAchR entre células cancerosas y sanas, obtenidas de muestras de cáncer de colon y cáncer de próstata. El proyecto financiado con fondos europeos nAChRs-CRC-PCa-IF-RI investigará el papel fisiopatológico de los nAchR en el cáncer colorrectal y el cáncer de próstata. Los objetivos del proyecto son identificar los nAchR implicados en el cáncer de colon y el cáncer de próstata, caracterizar el papel de los nAchR en la migración, proliferación e invasión, y estudiar los efectos de dupα7, una subunidad de nAchR, en la antiangiogénesis. El equipo también estudiará la influencia de la quimioterapia en la expresión de los nAchR.
Objetivo
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.
Ámbito científico
Palabras clave
Programa(s)
Régimen de financiación
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinador
3012 Bern
Suiza