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

Nature Communications
Alexandra AvgustinovaClare M Isacke

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.

References

Mar 1, 1991·Clinical & Experimental Metastasis·C J AslaksonF R Miller
Jun 1, 1990·Molecular and Cellular Biology·C M IsackeI S Trowbridge
Oct 5, 2001·The Journal of Biological Chemistry·K IshiguroT Muramatsu
Jun 29, 2002·Cellular Immunology·B C SchaeferR M Kedl
Mar 6, 2004·Cancer Metastasis Reviews·Liliana Attisano, Etienne Labbé
Dec 22, 2004·Mechanisms of Ageing and Development·Gerold UntergasserPeter Berger
Feb 11, 2005·Proceedings of the National Academy of Sciences of the United States of America·Howard Y ChangMarc J van de Vijver
Nov 18, 2005·Cytokine & Growth Factor Reviews·Brian Bierie, Harold L Moses
Jan 21, 2006·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Jorge S Reis-FilhoAlan Ashworth
Mar 31, 2006·Nature Reviews. Cancer·Raghu Kalluri, Michael Zeisberg
Nov 16, 2006·Cancer Biology & Therapy·Hikaru SugimotoRaghu Kalluri
Jan 15, 2008·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Nicole SimonaviciusClare M Isacke
Mar 28, 2008·BMC Cell Biology·David RobertsonClare M Isacke
Apr 29, 2008·Nature Medicine·Greg FinakMorag Park
Jul 17, 2008·Nature Reviews. Molecular Cell Biology·Matthias Schäfer, Sabine Werner
Sep 6, 2008·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Yuanmei LouShoukat Dedhar
Sep 9, 2008·International Journal of Cancer. Journal International Du Cancer·Olivier De WeverMarc Bracke
Nov 20, 2008·Science Signaling·Nancy R Gough
Mar 10, 2010·Experimental Cell Research·Kristian Pietras, Arne Ostman
May 19, 2010·Proceedings of the National Academy of Sciences of the United States of America·Sherene LoiChristos Sotiriou
Nov 3, 2010·Proceedings of the National Academy of Sciences of the United States of America·Yasushi KojimaAkira Orimo
Jun 15, 2011·Proceedings of the National Academy of Sciences of the United States of America·Lorenza CianiPatricia C Salinas
Nov 22, 2011·Cancer Metastasis Reviews·Paolo Cirri, Paola Chiarugi
Jan 11, 2012·Molecular Cancer Research : MCR·Shin YoshiokaKanako Hayashi
Mar 15, 2012·Nature Communications·Alfiya AkhmetshinaJörg H W Distler
Apr 11, 2012·The Journal of Pathology·Samantha A SimpkinsValerie Speirs
Dec 21, 2012·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Kuldeep KumawatReinoud Gosens
Jan 8, 2013·Cell Stem Cell·C Florian BentzingerMichael A Rudnicki
Jan 11, 2013·Proceedings of the National Academy of Sciences of the United States of America·Shuyu RenJeremy S Duffield
Feb 5, 2013·Biochemical Pharmacology·Kim H T Paraiso, Keiran S M Smalley

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Citations

Feb 18, 2017·Molecular Cancer·Pramudita R Prasetyanti, Jan Paul Medema
Mar 17, 2018·Nature Reviews. Cancer·Christina H StueltenDenise J Montell
Dec 1, 2017·Nucleic Acids Research·Anders SundqvistPeter Ten Dijke
Nov 9, 2017·Journal of Translational Medicine·Giacomo MiserocchiToni Ibrahim
Aug 24, 2016·Nature Reviews. Cancer·Raghu Kalluri
Apr 20, 2018·Molecular & Cellular Proteomics : MCP·Wei WuAlbert J R Heck
Sep 12, 2018·The Journal of Clinical Investigation·Yingying WangJianhua Wang
Sep 13, 2018·The Journal of Pathology. Clinical Research·Yihong WangMurray B Resnick
Nov 23, 2018·Cancer Metastasis Reviews·J M Houthuijzen, J Jonkers
Feb 9, 2019·International Journal of Cancer. Journal International Du Cancer·Martin NurmikElisabeth Letellier
Mar 10, 2018·Scientific Reports·Amy F MartinezNirmala Ramanujam
Jul 5, 2019·Journal of Cellular Biochemistry·Lihui LanChenghai Zhao
Aug 25, 2019·Stem Cell Research & Therapy·Vasudeva BhatAfshin Raouf
May 10, 2019·Frontiers in Immunology·George TzanakakisDragana Nikitovic
Jan 26, 2020·Nature Reviews. Cancer·Erik SahaiZena Werb
Jan 16, 2020·Molecular Cancer·Zhonghua MaJiafu Ji
Jan 30, 2020·British Journal of Cancer·Elisa D'ArcangeloAlison P McGuigan
Sep 29, 2020·Frontiers in Oncology·Margaux SalaFrédéric Saltel
Aug 25, 2016·Cell & Bioscience·Dietmar ZechnerBrigitte Vollmar
Aug 11, 2016·Cell and Tissue Research·Yoshihiro Mezawa, Akira Orimo
Aug 28, 2020·Frontiers in Oncology·Océane CampionJérôme Devy
Jul 31, 2016·Cell and Tissue Research·Sanya-Eduarda Kuzet, Cedric Gaggioli
Aug 2, 2017·International Journal of Molecular Sciences·Jee-Heun KimJeong-Seok Nam
Jun 6, 2018·Proceedings of the National Academy of Sciences of the United States of America·Sharathchandra ArandkarMoshe Oren
Nov 17, 2019·Journal of Clinical Medicine·Tom J HarryvanSjoerd H van der Burg
Feb 23, 2020·Frontiers in Cell and Developmental Biology·Emma H van Schie, Renée van Amerongen
Nov 24, 2020·Journal of Experimental & Clinical Cancer Research : CR·Dongmei YangHonggang Yu

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Methods Mentioned

BETA
nuclear translocation
FCS
Assay

Software Mentioned

Image J
R
SDS
Java Treeview
Cluster
Graphpad Prism
SPSS
limma

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