H2020Индивидуална стипендия2022–2024

nAChRs-CRC-PCa-IF-RI · Nicotinic Acetylcholine Receptors nAChRs in Prostate and Colon Cell Cancer: pharmacology, mechanism, cellular (mal)function

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2022-04-01 → 2024-03-31
Финансиране от ЕС: 203 149 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Никотиновите ацетилхолинови рецептори, по-конкретно под единица $\alpha 5$, се изследват в рака на простатата и дебелото черво. Това помага да се разбере как тютюневият дим стимулира разпространението и размножаването на раковите клетки.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Nicotinic Acetylcholine Receptors nAChRs in Prostate and Colon Cell Cancer: pharmacology, mechanism, cellular (mal)function

• Tobacco exposure is a very well-known risk factor in cancer. One of its proposed mechanisms is through the activation of various nicotinic acetylcholine receptors nAChR, and consequently inducing and promoting cancer through different mechanisms. In lung cancer nicotine and its metabolites increase cell proliferation, invasion, migration, epithelial to mesenchymal transition (EMT) and activate specific signaling cascades principally through α7 and α9 nAChR subunits. And although current data associates cigarette smoking with prostate (PCa) and colon cancer (CRC), no study had addressed the question of whether nAChR contributed to this effect and the underlying signaling events. • In this context, the research projects principal aim was to investigate nAChRs in the physiology/pathophysiology of CRC and PCa, where I explored the contribution of specific nAChRs to cancers hallmark functions, investigate the mechanism(s), and the respective signaling cascade(s) involved. Thus, first I set to (i) identify and characterize the role of nAChR in PCa and CRC, and (ii) investigate the role of nAChRs in migration, proliferation and invasion in CRC and PCa cancer cell lines. Here it was found that a specific subunit, the α5 nAChR subunit, was overexpressed amongst other subunits in different types of cancers, and that it was responsible for nicotine’s promotion of proliferation and migration in cell lines of breast, colon, and prostate cancer origins. Furthermore, the α5 subunit was also key for nicotine’s-promoted expression of cancer molecular markers and immune regulatory proteins. Moreover, a specific polymorphism in this subunit, which is known to be related to nicotine administration, dependence, and lung cancer, caused an inherent increase in proliferation and migration in colon cancer cells. Through a mechanism involving G-protein signaling. Taken together, our results indicate that nicotine-induced pro-oncogenic effects in PCa and CRC are mediated via the α5 subunit, adding to its characterization as a possible druggable target to target cancer.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

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.

Оригинален текст от CORDIS (на английски).

Участници

UNIVERSITAET BERN · BernКоординаторШвейцария