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MetCAF SIGNED

Uncovering the Role of Cancer Associated Fibroblasts in Facilitating Breast Cancer Metastasis

Total Cost €

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EC-Contrib. €

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Partnership

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Project "MetCAF" data sheet

The following table provides information about the project.

Coordinator
TEL AVIV UNIVERSITY 

Organization address
address: RAMAT AVIV
city: TEL AVIV
postcode: 69978
website: http://www.tau.ac.il/

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Israel [IL]
 Project website https://netaerez.tau.ac.il/index.php
 Total cost 1˙281˙958 €
 EC max contribution 1˙281˙958 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-STG
 Funding Scheme ERC-STG
 Starting year 2015
 Duration (year-month-day) from 2015-07-01   to  2021-06-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    TEL AVIV UNIVERSITY IL (TEL AVIV) coordinator 1˙281˙958.00

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 Project objective

Mortality from breast cancer is almost exclusively a result of tumor metastasis. Since advanced metastatic cancers are usually fatal, understanding the biology of tumor metastasis is the most significant challenge in cancer research today. It has become clear that the microenvironment of tumors is crucial in supporting tumor growth. Nevertheless, the role of the metastatic microenvironment in facilitating metastatic colonization is largely unknown. We recently uncovered a novel role for Cancer-Associated Fibroblasts (CAFs) in mediating tumor-promoting inflammation. However, the role of CAFs in the formation of a permissive metastatic niche that enables the growth of disseminated tumor cells is unresolved. I propose to systematically investigate, for the first time, the molecular changes in CAFs that facilitate metastases formation, which may lead to the discovery of novel targets for cancer therapeutics. To achieve this goal, I will integrate tumor biology knowledge and the unique expertise of my lab: we will combine novel mouse models of spontaneous lung metastasis of breast cancer, imitating the clinical setting, with multi-transgenic reporter mice that enable origin tracing and unbiased analysis of fibroblast sub-populations. By performing a comprehensive molecular and functional characterization of fibroblast co-evolution during metastases formation and analysis of breast cancer patient cohorts, we will uncover the dynamic changes in CAFs at the metastatic niche, identify the origin of metastatic CAFs, and elucidate the signaling pathways that govern their functional role in breast cancer metastasis. Molecular understanding of the early stages of tumor metastasis is an essential prerequisite for the discovery of novel therapeutic targets. Achievement of the proposed goals will shed light on a central conundrum in cancer biology and open new horizons for the development of novel therapeutics that will transform cancer into a chronic, yet manageable disease.

 Publications

year authors and title journal last update
List of publications.
2018 Yael Raz, Noam Cohen, Ophir Shani, Rachel E. Bell, Sergey V. Novitskiy, Lilach Abramovitz, Carmit Levy, Michael Milyavsky, Leonor Leider-Trejo, Harold L. Moses, Dan Grisaru, Neta Erez
Bone marrow–derived fibroblasts are a functionally distinct stromal cell population in breast cancer
published pages: 3075-3093, ISSN: 0022-1007, DOI: 10.1084/jem.20180818
The Journal of Experimental Medicine 215/12 2020-03-11
2019 Ophir Shani, ProfileYael Raz, Or Megides, Hila Shacham, Noam Cohen, Dana Silverbush, Lea Monteran, Roded Sharan, Ilan Tsarfaty, Neta Erez
Evolution of metastases-associated fibroblasts in the lung microenvironment is driven by stage-specific transcriptional plasticity
published pages: , ISSN: , DOI: 10.1101/778936
2020-03-11
2019 Lea Monteran, Neta Erez
The Dark Side of Fibroblasts: Cancer-Associated Fibroblasts as Mediators of Immunosuppression in the Tumor Microenvironment
published pages: , ISSN: 1664-3224, DOI: 10.3389/fimmu.2019.01835
Frontiers in Immunology 10 2020-03-11
2019 Nour Ershaid, Yoray Sharon, Hila Doron, Yael Raz, Ophir Shani, Noam Cohen, Lea Monteran, Leonor Leider-Trejo, Amir Ben-Shmuel, Muhammad Yassin, Motti Gerlic, Adit Ben-Baruch, Metsada Pasmanik-Chor, Roni Apte, Neta Erez
NLRP3 inflammasome in fibroblasts links tissue damage with inflammation in breast cancer progression and metastasis
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-019-12370-8
Nature Communications 10/1 2020-03-11
2017 N Cohen, O Shani, Y Raz, Y Sharon, D Hoffman, L Abramovitz, N Erez
Fibroblasts drive an immunosuppressive and growth-promoting microenvironment in breast cancer via secretion of Chitinase 3-like 1
published pages: , ISSN: 0950-9232, DOI: 10.1038/onc.2017.65
Oncogene 2020-03-11

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