Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/22445
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dc.contributor.authorEckhardt, Bedrich L-
dc.contributor.authorCao, Yuan-
dc.contributor.authorRedfern, Andrew D-
dc.contributor.authorChi, Lap Hing-
dc.contributor.authorBurrows, Allan D-
dc.contributor.authorRoslan, Suraya-
dc.contributor.authorSloan, Erica K-
dc.contributor.authorParker, Belinda S-
dc.contributor.authorLoi, Sherene-
dc.contributor.authorUeno, Naoto T-
dc.contributor.authorLau, Peter K H-
dc.contributor.authorLatham, Bruce-
dc.contributor.authorAnderson, Robin L-
dc.date2020-01-15-
dc.date.accessioned2020-01-20T05:24:55Z-
dc.date.available2020-01-20T05:24:55Z-
dc.date.issued2020-03-15-
dc.identifier.citationCancer research 2020; 80(6): 1304-1315-
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/22445-
dc.description.abstractMetastasis is the major cause of death in cancer patients; with no therapeutic cure, treatments remain largely palliative. As such, new targets and therapeutic strategies are urgently required. Here we show that bone morphogenetic protein-4 (BMP4) blocks metastasis in animal models of breast cancer and predicts improved survival in patients. In preclinical models of spontaneous metastasis, BMP4 acted as an autocrine mediator to modulate a range of known metastasis-regulating genes, including SMAD7, via activation of canonical BMP-SMAD signaling. Restored BMP4 expression, or therapeutically administered BMP4 protein, blocked metastasis and increased survival by sensitising cancer cells to anoikis, thereby reducing the number of circulating tumour cells. Gene silencing of BMP4, or its downstream mediator SMAD7, reversed this phenotype. Administration of recombinant BMP4 markedly reduced spontaneous metastasis to lung and bone. Elevated levels of BMP4 and SMAD7 were prognostic for improved recurrence-free survival and overall survival in breast cancer patients, indicating the importance of canonical BMP4 signaling in the suppression of metastasis and highlighting new avenues for therapy against metastatic disease.-
dc.language.isoeng-
dc.titleActivation of canonical BMP4-SMAD7 signaling suppresses breast cancer metastasis.-
dc.typeJournal Article-
dc.identifier.journaltitleCancer research-
dc.identifier.affiliationTranslational Breast Cancer Program, Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia-
dc.identifier.affiliationResearch, Peter MacCallum Cancer Centre-
dc.identifier.affiliationLaboratory for Cancer Medicine, Western Australian Institute for Medical Research..-
dc.identifier.affiliationMetastasis Research Laboratory, Olivia Newton-John Cancer Wellness & Research Centre-
dc.identifier.affiliationOlivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia-
dc.identifier.affiliationDrug Discovery Biology Theme, Monash University-
dc.identifier.affiliationCancer immunology and Therapeutics Programs, Peter MacCallum Cancer Centre-
dc.identifier.affiliationDivision of Research and Clinical Medicine, Peter MacCallum Cancer Centre-
dc.identifier.affiliationBreast Medical Oncology, The University of Texas MD Anderson Cancer Center-
dc.identifier.affiliationMedical Oncology, Peter MacCallum Cancer Centre-
dc.identifier.affiliationPathology, PathWest-
dc.identifier.doi10.1158/0008-5472.CAN-19-0743-
dc.identifier.orcid0000-0002-3402-3900-
dc.identifier.orcid0000-0001-5544-8054-
dc.identifier.orcid0000-0003-0983-3474-
dc.identifier.orcid0000-0002-8333-1926-
dc.identifier.orcid0000-0001-6137-9171-
dc.identifier.orcid0000-0002-0166-7275-
dc.identifier.orcid0000-0003-1071-7956-
dc.identifier.orcid0000-0003-0595-1414-
dc.identifier.pubmedid31941699-
dc.type.austinJournal Article-
local.name.researcherAnderson, Robin L
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.cerifentitytypePublications-
item.fulltextNo Fulltext-
item.grantfulltextnone-
item.languageiso639-1en-
item.openairetypeJournal Article-
crisitem.author.deptOlivia Newton-John Cancer Research Institute-
Appears in Collections:Conferences
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