INVASION SCREENING · Gene silencing-based functional screening for genes regulating invasion in human cancer cells
6РП — Действия „Мария Кюри“
- Период
- 2006-04-01 → 2008-03-31
- Финансиране от ЕС
- 159 614 €
- Участници
- 2
- Схема
- EIF
Линиите свързват координатора с партньорите.
Накратко на български
Протеините от семейството Rho GTPases (като RhoA, RhoB и RhoC) регулират как раковите клетки се движат и разпространяват в тъканите. Разбирането на тези процеси помага при търсенето на нови методи за терапевтична намеса при рак на простатата.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Final Activity Report Summary - INVASION SCREENING (Gene silencing-based functional screening for genes regulating invasion in human cancer cells)
An analysis of the involvement of the Rho GTPases family of proteins in cancer cell migration and invasion has been carried out. The study has helped in the understanding of the role of this family of proteins in different processes during cancer progression, especially in the dissemination of cancer cells through tissues. In particular, results obtained during the course of the project have determined specific functions for closely related members of the family as are RhoA, RhoB and RhoC, highlighting the importance of specificity within this family of proteins in cell function regulation. This is not only relevant to posterior studies but also for the possible cancer therapeutic intervention targeting this class of proteins. The work also joins the efforts by other research laboratories on understanding the cellular and molecular basis behind human prostate cancer, one of the most common cancers in men, that frequently develops with aggressive metastasis. Different techniques have being developed and improved for use in the host laboratory and by the scientific community in general. Special relevance have the techniques modelling 3D migration and invasion in vitro, for the possibility to carry out detailed cellular studies in the laboratory in models that try to resemble tumour cells dissemination in vivo. As a result of the work and the knowledge about Rho GTPases and cancer accumulated by the host laboratory and acquired by the fellow, two invited review articles have been produced for international scientific journals that will encourage discussion within the cancer and Rho GTPases field and bring the topic to the general scientific community.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
The proposed project uses a RNA interference-based loss-of-function genetic screen in cancer cells to identify and study proteins with a role in tumor cell invasion. A retroviral vector-based human RNAi library and a set of syntethics iRNAs will be used to suppress the expression of specific genes in cancer cells. The library targets around 8000 human genes selected for their association with cancer and other human diseases and include entire gene families suitable for being therapeutical targets. The genes in the set have been selected for their possible implication in actin dynamics and migration. I will check for abnormal invasion phenotypes on these cells in a modification of a classical cell-based in vitro invasion assay on 3-D collagen matrices in resp onse to hepatocyte growth factor/scatter factor (HGF/SF), a protein that induces the migration and invasion of various types of cancer cells. For this study I plan to use initially the PC-3 human prostate cancer cell line that invade well in response to HG F and is suitable for the use of RNAi in gene silencing. Later on results obtained will be confirmed in another model cell line, the BE colon carcinoma cell line, as well as in another prostate cancer line with a different metastatic potential. At the beginning the invasion system will be exploited to analyse in detail the contribution to tumour invasion of the Rho family of small GTPases followed later on with a high-throughput screen using a subset of RNAi constructs targeting all the human protein kinases and a selective large-scale screen with the whole library to identify new regulators of cancer cell invasion that would potentially serve as new therapeutical targets against cancer. This project will also complete the researcher and apos;s expertise in basic cancer research and extend it to the field of tumour metastasis, with scope to continue the researcher and apos;s career with the findings obtained from the project in a future independent position.
Оригинален текст от CORDIS (на английски).
Участници
- KING'S COLLEGE LONDON BUSINESS LTD · LONDONКоординаторОбединеното кралство
- LUDWIG INSTITUTE FOR CANCER RESEARCH · LONDONОбединеното кралство
Връзки
Данни: CORDIS, © Европейски съюз