H2020Индивидуална стипендия2021–2023

PROMIGREX · Mechanical regulation of cell migration by Piezo1 and its implications in epithelial cell turnover

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

Период: 2021-04-01 → 2023-05-31
Финансиране от ЕС: 212 934 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Каналът Piezo1 регулира как епителните клетки се движат, делят се и умират при механично натиск или разтягане. Разбирането на тези механизми помага при изучаването на рака, астмата и възпалителните заболявания на червата.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

Mechanical regulation of cell migration by Piezo1 and its implications in epithelial cell turnover

Epithelial cells turn over by cell death and division at some of the fastest rates in the body but must maintain constant numbers while doing so. The rates of cell division must match the rates of cell death or cells could amass into tumours or disappear completely, destroying the barrier they provide to all the organs they encase. This coupling has far-reaching consequences for health and disease, because barrier defects due to cell loss are a hallmark of prevalent diseases like asthma or inflammatory bowel disease, and cell accumulation drives cancer growth. Therefore, identifying the mechanisms controlling epithelial cell turnover may offer new therapeutical opportunities. Mechanical forces link cell death and division; where crowding activates cells to extrude from the epithelial layer and die and stretch triggers rapid cells to rapidly enter mitosis. Critically, both mechano-responses require the stretch- activated cationic channel Piezo1. The overarching goal of PROMIGREX was to identify the mechanisms by which this channel controls cell division, migration, and death in response to mechanical signals. Specifically, this project aimed at describing how Piezo1 detects cell-cell collisions and redirects migration, how it detects forces and triggers severing of the thin connection between dividing cells, and how its mutations in cancer affect these processes.

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

Цел на проекта

Cancers arise in cell types that turnover by proliferation and death at highest rates, likely because these rates become unbalanced. Our group found that mechanical forces control both processes in epithelia: stretch activates proliferation whereas crowding activates cell extrusion and death. However, it was unclear what causes crowding and stretching forces in epithelia. I will investigate if cell migration from sites of proliferation drives the conveyor belt forces that control stretch-induced cell division and crowding-induced death. If so, the rate of cell migration could drive the rate of cell turnover and, hence, the propensity for a tissue to become cancerous. While my host lab has already identified roles for the stretch- activated ion channel Piezo1 in controlling proliferation and extrusion, based on preliminary compelling findings, I will determine if it also controls cell migration from sites of division. To do so, I will use established models in cell culture and mouse gut and develop an in vivo zebrafish gut model for homeostatic epithelial cell turnover. Additionally, I will test if frequent Piezo1 mutations in colon cancer impact cell proliferation, migration, and death. If my hypothesis is correct, I will reveal a new, unexpected role for cell migration in not only normal epithelial cell turnover but also in carcinogenesis. Should Piezo1 act as a central transducer of mechano-chemical coupling, it could provide a new target for therapeutics.

Оригинален текст от CORDIS (на английски).

Участници

KING'S COLLEGE LONDON · LondonКоординаторОбединеното кралство