Tumour cell-derived Wnt7a recruits and activates fibroblasts to promote tumour aggressiveness

Alexandra Avgustinova, Marjan Iravani, David Robertson, Antony Fearns, Qiong Gao, Pamela Klingbeil, Andrew M. Hanby, Valerie Speirs, Erik Sahai, Fernando Calvo and Clare M. Isacke ()
Additional contact information
Alexandra Avgustinova: The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research
Marjan Iravani: The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research
David Robertson: The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research
Antony Fearns: The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research
Qiong Gao: The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research
Pamela Klingbeil: The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research
Andrew M. Hanby: Leeds Institute of Cancer and Pathology, University of Leeds
Valerie Speirs: Leeds Institute of Cancer and Pathology, University of Leeds
Erik Sahai: Tumour Cell Biology Laboratory, Francis Crick Institute, 44 Lincoln's Inn Fields
Fernando Calvo: Tumour Cell Biology Laboratory, Francis Crick Institute, 44 Lincoln's Inn Fields
Clare M. Isacke: The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research

Nature Communications, 2016, vol. 7, issue 1, 1-14

Abstract: Abstract Stromal fibroblast recruitment to tumours and activation to a cancer-associated fibroblast (CAF) phenotype has been implicated in promoting primary tumour growth and progression to metastatic disease. However, the mechanisms underlying the tumour:fibroblast crosstalk that drive the intertumoural stromal heterogeneity remain poorly understood. Using in vivo models we identify Wnt7a as a key factor secreted exclusively by aggressive breast tumour cells, which induces CAF conversion. Functionally, this results in extracellular matrix remodelling to create a permissive environment for tumour cell invasion and promotion of distant metastasis. Mechanistically, Wnt7a-mediated fibroblast activation is not dependent on classical Wnt signalling. Instead, we demonstrate that Wnt7a potentiates TGFβ receptor signalling both in 3D in vitro and in vivo models, thus highlighting the interaction between two of the key signalling pathways in development and disease. Importantly, in clinical breast cancer cohorts, tumour cell Wnt7a expression correlates with a desmoplastic, poor-prognosis stroma and poor patient outcome.

Date: 2016
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/ncomms10305 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10305

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms10305

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().