H2020Индивидуална стипендия2016–2018

GENMETASTEM · GENOMIC AND METABOLIC REGULATION OF METASTATIC CANCER STEM CELLS

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

Период: 2016-09-01 → 2018-08-31
Финансиране от ЕС: 183 455 €
Участници: 1
Схема: MSCA-IF-EF-ST

Линиите свързват координатора с партньорите.

Накратко на български

Ракните стволови клетки и начинът, по който те се движат и променят формата си, се анализират при карциноми и меланоми. Разбирането на тези процеси помага да се разбере защо ракът се разпространява към други органи и проявява устойчивост към терапиите.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

GENOMIC AND METABOLIC REGULATION OF METASTATIC CANCER STEM CELLS

The major problems of cancer disease are 1) the relapse and resistance to current therapies that have been associated with the presence of cancer stem cells (CSCs) and 2) the spread of invasive metastatic cells to distant organs that is responsible for most cancer-associated deaths. CSCs represent a tumour cell subpopulation with the ability to self-renew and differentiate into non-CSCs. In carcinoma cells, the acquisition of stemness properties has been closely related to epithelial-mesenchymal transition (EMT), a key process in cancer invasion and metastasis. However, although EMT can be considered a process that generates CSCs, the connection between CSCs and metastasis is not yet well understood. Interestingly, in melanoma, a non-epithelial tumour, transition from elongated-mesenchymal to amoeboid mode of movement (MAT) driven by Rho-ROCK signalling has been associated with increased stemness. Nevertheless, how very contractile cells regulate genes involved in EMT, tumour initiation and metastatic spread remains unexplored. Moreover, it is not known if the same genes regulate all these processes. As increasing cellular plasticity via EMT in carcinoma cells or via MAT in melanoma cells correlates with increasing stemness, we hypothesized a molecular link between the pathways regulating both migration and stemness abilities. Therefore, the main goal of this proposal has been to understand how tumour cells can acquire stem cell traits to successfully metastasize and how this can be regulated by the actomyosin cytoskeletal by using an interdisciplinary approach that combines state-of-the-art techniques in molecular and cellular biology, biochemistry, in vivo imaging and animal models. This has allow us to identify key important genes regulating both stemness traits and metastatic spread and identified prognostic markers of distant relapse and patient survival.

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

Цел на проекта

The major causes of cancer deaths are relapse and resistance to current therapies associated with the presence of cancer stem cells (CSCs) and metastatic growth in distant organs. CSCs have the ability to self-renew and differentiate in non-CSCs. In breast cancer, acquisition of stemness properties has been closely related to epithelial-mesenchymal transition (EMT), a key process in cancer invasion and metastasis triggered via Rho-ROCK mediated actomyosin contractility. Interestingly, in melanoma, transition from elongated-mesenchymal to amoeboid mode of movement (MAT) driven by Rho-ROCK signalling has been associated with increased stemness. Furthermore, preliminary data from host lab shows that actomyosin cytoskeletal regulates glutamine metabolism in both melanoma and breast cancer cells. Metabolic cues participate in stem cell self-renewal regulation, suggesting that, in very contractile cells, the regulation of EMT, metastatic spread and tumour initiation might be functionally linked to stemness via metabolic clues. Nevertheless, how very contractile cells regulate genes involved in all these processes remains unexplored. As increasing contractility via EMT in carcinoma cells or via MAT in melanoma cells correlates with increasing stemness, we hypothesize a molecular link between the pathways regulating both migration and stemness abilities, which will be maintained across tumour types (from carcinoma to melanoma). The main goal of this proposal is to understand how tumour cells can acquire stem cell traits to successfully metastasize and how this can be regulated by the actomyosin cytoskeletal by using an interdisciplinary approach that combines state-of-the-art techniques in molecular and cellular biology, biochemistry, in vivo imaging and animal models. This will allow to identify key important genes regulating both stemness traits and metastatic spread with the ultimate goal of unravelling novel drug targets and prognostic markers of distant relapse.

Оригинален текст от CORDIS (на английски).

Участници

KING'S COLLEGE LONDON · LondonКоординаторОбединеното кралство