Show simple item record

dc.contributor.authorGreen, Darrell; orcid: 0000-0002-0217-3322
dc.contributor.authorEyre, Heather
dc.contributor.authorSingh, Archana; orcid: 0000-0002-5027-4582
dc.contributor.authorTaylor, Jessica T.
dc.contributor.authorChu, Jason
dc.contributor.authorJeys, Lee
dc.contributor.authorSumathi, Vaiyapuri
dc.contributor.authorCoonar, Aman
dc.contributor.authorRassl, Doris
dc.contributor.authorBabur, Muhammad
dc.contributor.authorForster, Duncan
dc.contributor.authorAlzabin, Saba
dc.contributor.authorPonthan, Frida
dc.contributor.authorMcMahon, Adam
dc.contributor.authorBigger, Brian
dc.contributor.authorReekie, Tristan
dc.contributor.authorKassiou, Michael
dc.contributor.authorWilliams, Kaye
dc.contributor.authorDalmay, Tamas; orcid: 0000-0003-1492-5429
dc.contributor.authorFraser, William D.; orcid: 0000-0003-0556-3358; email: w.fraser@uea.ac.uk
dc.contributor.authorFinegan, Katherine G.; orcid: 0000-0003-2885-0122; email: k.g.finegan@manchester.ac.uk
dc.date.accessioned2021-07-13T15:20:17Z
dc.date.available2021-07-13T15:20:17Z
dc.date.issued2020-07-13
dc.date.submitted2020-03-17
dc.identifierhttps://chesterrep.openrepository.com/bitstream/handle/10034/625252/41388_2020_Article_1379.pdf?sequence=2
dc.identifierhttps://chesterrep.openrepository.com/bitstream/handle/10034/625252/additional-files.zip?sequence=3
dc.identifierhttps://chesterrep.openrepository.com/bitstream/handle/10034/625252/41388_2020_Article_1379_nlm.xml?sequence=4
dc.identifier.citationOncogene, volume 39, issue 33, page 5553-5569
dc.identifier.urihttp://hdl.handle.net/10034/625252
dc.descriptionFrom Springer Nature via Jisc Publications Router
dc.descriptionHistory: received 2020-03-17, rev-recd 2020-05-24, accepted 2020-06-23, registration 2020-06-24, pub-electronic 2020-07-13, online 2020-07-13, pub-print 2020-08-13
dc.descriptionPublication status: Published
dc.descriptionFunder: Friends of Rosie
dc.descriptionFunder: THRT, Big C, Paget's Association
dc.description.abstractAbstract: Metastasis is the leading cause of cancer-related death. This multistage process involves contribution from both tumour cells and the tumour stroma to release metastatic cells into the circulation. Circulating tumour cells (CTCs) survive circulatory cytotoxicity, extravasate and colonise secondary sites effecting metastatic outcome. Reprogramming the transcriptomic landscape is a metastatic hallmark, but detecting underlying master regulators that drive pathological gene expression is a key challenge, especially in childhood cancer. Here we used whole tumour plus single-cell RNA-sequencing in primary bone cancer and CTCs to perform weighted gene co-expression network analysis to systematically detect coordinated changes in metastatic transcript expression. This approach with comparisons applied to data collected from cell line models, clinical samples and xenograft mouse models revealed mitogen-activated protein kinase 7/matrix metallopeptidase 9 (MAPK7/MMP9) signalling as a driver for primary bone cancer metastasis. RNA interference knockdown of MAPK7 reduces proliferation, colony formation, migration, tumour growth, macrophage residency/polarisation and lung metastasis. Parallel to these observations were reduction of activated interleukins IL1B, IL6, IL8 plus mesenchymal markers VIM and VEGF in response to MAPK7 loss. Our results implicate a newly discovered, multidimensional MAPK7/MMP9 signalling hub in primary bone cancer metastasis that is clinically actionable.
dc.languageen
dc.publisherNature Publishing Group UK
dc.rightsLicence for this article: http://creativecommons.org/licenses/by/4.0/
dc.sourcepissn: 0950-9232
dc.sourceeissn: 1476-5594
dc.subjectArticle
dc.subject/631/67/1344
dc.subject/631/80/304
dc.subject/631/337/2019
dc.subject/13/89
dc.subject/13/62
dc.subject/38/91
dc.subject/82/80
dc.subject/64/60
dc.subject/59/78
dc.subject/59/5
dc.subjectarticle
dc.titleTargeting the MAPK7/MMP9 axis for metastasis in primary bone cancer
dc.typearticle
dc.date.updated2021-07-13T15:20:17Z
dc.date.accepted2020-06-23


Files in this item

Thumbnail
Name:
41388_2020_Article_1379.pdf
Size:
3.128Mb
Format:
PDF
Thumbnail
Name:
additional-files.zip
Size:
1.706Mb
Format:
Unknown
Thumbnail
Name:
41388_2020_Article_1379_nlm.xml
Size:
132.0Kb
Format:
XML

This item appears in the following Collection(s)

Show simple item record