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  4. TGF beta-mediated MMP13 secretion drives myoepithelial cell dependent breast cancer progression
 
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research article

TGF beta-mediated MMP13 secretion drives myoepithelial cell dependent breast cancer progression

Gibson, Shayin V.
•
Tomas Bort, Elena
•
Rodriguez-Fernandez, Lucia
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March 2, 2023
Npj Breast Cancer

Ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive breast cancer. Virtually all women with DCIS are treated, despite evidence suggesting up to half would remain with stable, non-threatening, disease. Overtreatment thus presents a pressing issue in DCIS management. To understand the role of the normally tumour suppressive myoepithelial cell in disease progression we present a 3D in vitro model incorporating both luminal and myoepithelial cells in physiomimetic conditions. We demonstrate that DCIS-associated myoepithelial cells promote striking myoepithelial-led invasion of luminal cells, mediated by the collagenase MMP13 through a non-canonical TGF beta - EP300 pathway. In vivo, MMP13 expression is associated with stromal invasion in a murine model of DCIS progression and is elevated in myoepithelial cells of clinical high-grade DCIS cases. Our data identify a key role for myoepithelial-derived MMP13 in facilitating DCIS progression and point the way towards a robust marker for risk stratification in DCIS patients.

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Type
research article
DOI
10.1038/s41523-023-00513-6
Web of Science ID

WOS:000942808900001

Author(s)
Gibson, Shayin V.
•
Tomas Bort, Elena
•
Rodriguez-Fernandez, Lucia
•
Allen, Michael D.
•
Gomm, Jennifer J.
•
Goulding, Iain
•
Keller, Ulrich Auf Dem
•
Agnoletto, Andrea  
•
Brisken, Cathrin  
•
Peck, Barrie
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Date Issued

2023-03-02

Publisher

NATURE PORTFOLIO

Published in
Npj Breast Cancer
Volume

9

Issue

1

Start page

9

Subjects

Oncology

•

carcinoma in-situ

•

growth-factor requirements

•

human mammary-gland

•

collagenase-3 expression

•

alpha-v-beta-6 integrin

•

tumor microenvironment

•

collective invasion

•

epithelial-cells

•

activation

•

dcis

Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
UPBRI  
Available on Infoscience
April 10, 2023
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/196821
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