Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/22445
Title: Activation of canonical BMP4-SMAD7 signaling suppresses breast cancer metastasis.
Authors: Eckhardt, Bedrich L;Cao, Yuan;Redfern, Andrew D;Chi, Lap Hing;Burrows, Allan D;Roslan, Suraya;Sloan, Erica K;Parker, Belinda S;Loi, Sherene;Ueno, Naoto T;Lau, Peter K H;Latham, Bruce;Anderson, Robin L
Affiliation: Translational Breast Cancer Program, Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
Research, Peter MacCallum Cancer Centre
Laboratory for Cancer Medicine, Western Australian Institute for Medical Research..
Metastasis Research Laboratory, Olivia Newton-John Cancer Wellness & Research Centre
Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
Drug Discovery Biology Theme, Monash University
Cancer immunology and Therapeutics Programs, Peter MacCallum Cancer Centre
Division of Research and Clinical Medicine, Peter MacCallum Cancer Centre
Breast Medical Oncology, The University of Texas MD Anderson Cancer Center
Medical Oncology, Peter MacCallum Cancer Centre
Pathology, PathWest
Issue Date: 15-Jan-2020
EDate: 2020-01-15
Citation: Cancer research 2020; online first: 15 January
Abstract: Metastasis 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.
URI: http://ahro.austin.org.au/austinjspui/handle/1/22445
DOI: 10.1158/0008-5472.CAN-19-0743
ORCID: 0000-0002-3402-3900
0000-0001-5544-8054
0000-0003-0983-3474
0000-0002-8333-1926
0000-0001-6137-9171
0000-0002-0166-7275
0000-0003-1071-7956
0000-0003-0595-1414
PubMed URL: 31941699
Type: Journal Article
Appears in Collections:Conference presentations

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