Imperial College London

DrLucaMagnani

Faculty of MedicineDepartment of Surgery & Cancer

Principal Research Fellow
 
 
 
//

Contact

 

+44 (0)20 7594 2808l.magnani CV

 
 
//

Location

 

137ICTEM buildingHammersmith Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Ferrari:2019:10.1038/s41467-018-07987-0,
author = {Ferrari, N and Ranftl, R and Chicherova, I and Slaven, ND and Moeendarbary, E and Farrugia, AJ and Lam, M and Semiannikova, M and Westergaard, MCW and Tchou, J and Magnani, L and Calvo, F},
doi = {10.1038/s41467-018-07987-0},
journal = {Nature Communications},
title = {Dickkopf-3 links HSF1 and YAP/TAZ signalling to control aggressive behaviours in cancer-associated fibroblasts},
url = {http://dx.doi.org/10.1038/s41467-018-07987-0},
volume = {10},
year = {2019}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Aggressive behaviours of solid tumours are highly influenced by the tumour microenvironment. Multiple signalling pathways can affect the normal function of stromal fibroblasts in tumours, but how these events are coordinated to generate tumour-promoting cancer-associated fibroblasts (CAFs) is not well understood. Here we show that stromal expression of Dickkopf-3 (DKK3) is associated with aggressive breast, colorectal and ovarian cancers. We demonstrate that DKK3 is a HSF1 effector that modulates the pro-tumorigenic behaviour of CAFs in vitro and in vivo. DKK3 orchestrates a concomitant activation of β-catenin and YAP/TAZ. Whereas β-catenin is dispensable for CAF-mediated ECM remodelling, cancer cell growth and invasion, DKK3-driven YAP/TAZ activation is required to induce tumour-promoting phenotypes. Mechanistically, DKK3 in CAFs acts via canonical Wnt signalling by interfering with the negative regulator Kremen and increasing cell-surface levels of LRP6. This work reveals an unpredicted link between HSF1, Wnt signalling and YAP/TAZ relevant for the generation of tumour-promoting CAFs.
AU - Ferrari,N
AU - Ranftl,R
AU - Chicherova,I
AU - Slaven,ND
AU - Moeendarbary,E
AU - Farrugia,AJ
AU - Lam,M
AU - Semiannikova,M
AU - Westergaard,MCW
AU - Tchou,J
AU - Magnani,L
AU - Calvo,F
DO - 10.1038/s41467-018-07987-0
PY - 2019///
SN - 2041-1723
TI - Dickkopf-3 links HSF1 and YAP/TAZ signalling to control aggressive behaviours in cancer-associated fibroblasts
T2 - Nature Communications
UR - http://dx.doi.org/10.1038/s41467-018-07987-0
UR - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000455354800027&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR - http://hdl.handle.net/10044/1/67895
VL - 10
ER -