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MetaRegulation SIGNED

Metabolic regulation of metastatic growth

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EC-Contrib. €

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Project "MetaRegulation" data sheet

The following table provides information about the project.

Coordinator
VIB VZW 

Organization address
address: RIJVISSCHESTRAAT 120
city: ZWIJNAARDE - GENT
postcode: 9052
website: www.vib.be

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 Belgium [BE]
 Total cost 2˙000˙000 €
 EC max contribution 2˙000˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2017-COG
 Funding Scheme ERC-COG
 Starting year 2018
 Duration (year-month-day) from 2018-06-01   to  2023-05-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    VIB VZW BE (ZWIJNAARDE - GENT) coordinator 2˙000˙000.00

Map

 Project objective

Metastatic growth of cancer cells requires extracellular matrix (ECM) production. The current understanding is that transcription factors regulate ECM production and thus metastatic growth by increasing the expression of collagen prolyl 4-hydroxylase (CP4H). In contrast, we recently discovered that metabolism regulates CP4H activity independently of the known transcription factors. Specifically, we found that loss of pyruvate metabolism inhibits CP4H activity and consequently ECM–dependent breast cancer cell growth. Based on this discovery we propose the novel concept that metabolism regulates metastatic growth by increasing ECM production.

In this project we will investigate the following questions: 1) What is the mechanism by which pyruvate regulates CP4H activity in breast cancer cells? To address this question we will investigate pyruvate metabolism and ECM production in 3D cultures of various breast cancer cell lines using 13C tracer analysis, metabolomics, and two-photon microscopy based ECM visualization. 2) How can this novel metabolic regulation be exploited to inhibit breast cancer-derived lung metastases growth? To address this question we will inhibit pyruvate metabolism in metastatic breast cancer mouse models using genetically modified cells and small molecules in combination with immuno- and chemotherapy. 3) How can this novel regulation be translated to different metastatic sites and cancers of different origin? To address this question we will determine the in vivo metabolism of breast cancer-, lung cancer-, and melanoma-derived liver and lung metastases (using metabolomics and 13C tracer analysis), and link it to ECM production (using two-photon microscopy based ECM visualization).

With this project we will deliver a novel concept by which metabolism regulates metastatic growth. In a long-term perspective we expect that targeting this novel metabolic regulation will pave the way for an unexplored approach to treat cancer metastases.

 Publications

year authors and title journal last update
List of publications.
2019 Sarah-Maria Fendt
Metabolic vulnerabilities of metastasizing cancer cells
published pages: , ISSN: 1741-7007, DOI: 10.1186/s12915-019-0672-2
BMC Biology 17/1 2020-01-28
2019 Kim Vriens, Stefan Christen, Sweta Parik, Dorien Broekaert, Kazuaki Yoshinaga, Ali Talebi, Jonas Dehairs, Carmen Escalona-Noguero, Roberta Schmieder, Thomas Cornfield, Catriona Charlton, Laura Romero-Pérez, Matteo Rossi, Gianmarco Rinaldi, Martin F. Orth, Ruben Boon, Axelle Kerstens, Suet Ying Kwan, Brandon Faubert, Andrés Méndez-Lucas, Charlotte C. Kopitz, Ting Chen, Juan Fernandez-Garcia, João A. G. Duarte, Arndt A. Schmitz, Patrick Steigemann, Mustapha Najimi, Andrea Hägebarth, Jo A. Van Ginderachter, Etienne Sokal, Naohiro Gotoh, Kwok-Kin Wong, Catherine Verfaillie, Rita Derua, Sebastian Munck, Mariia Yuneva, Laura Beretta, Ralph J. DeBerardinis, Johannes V. Swinnen, Leanne Hodson, David Cassiman, Chris Verslype, Sven Christian, Sylvia Grünewald, Thomas G. P. Grünewald, Sarah-Maria Fendt
Evidence for an alternative fatty acid desaturation pathway increasing cancer plasticity
published pages: 403-406, ISSN: 0028-0836, DOI: 10.1038/s41586-019-0904-1
Nature 566/7744 2019-06-06
2018 Ilaria Elia, Ginevra Doglioni, Sarah-Maria Fendt
Metabolic Hallmarks of Metastasis Formation
published pages: 673-684, ISSN: 0962-8924, DOI: 10.1016/j.tcb.2018.04.002
Trends in Cell Biology 28/8 2019-06-06
2019 Ilaria Elia, Matteo Rossi, Steve Stegen, Dorien Broekaert, Ginevra Doglioni, Marit van Gorsel, Ruben Boon, Carmen Escalona-Noguero, Sophie Torrekens, Catherine Verfaillie, Erik Verbeken, Geert Carmeliet, Sarah-Maria Fendt
Breast cancer cells rely on environmental pyruvate to shape the metastatic niche
published pages: 117-121, ISSN: 0028-0836, DOI: 10.1038/s41586-019-0977-x
Nature 568/7750 2019-06-06
2019 Ginevra Doglioni, Sweta Parik, Sarah-Maria Fendt
Interactions in the (Pre)metastatic Niche Support Metastasis Formation
published pages: , ISSN: 2234-943X, DOI: 10.3389/fonc.2019.00219
Frontiers in Oncology 9 2019-06-06

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