Open Access Gold as soon as Publ. Version/Full Text is submitted to ZB.
TRPS1 maintains luminal progenitors in the mammary gland by repressing SRF/MRTF activity.
Breast Cancer Res. 26:74 (2024)
The transcription factor TRPS1 is a context-dependent oncogene in breast cancer. In the mammary gland, TRPS1 activity is restricted to the luminal population and is critical during puberty and pregnancy. Its function in the resting state remains however unclear. To evaluate whether it could be a target for cancer therapy, we investigated TRPS1 function in the healthy adult mammary gland using a conditional ubiquitous depletion mouse model where long-term depletion does not affect fitness. Using transcriptomic approaches, flow cytometry and functional assays, we show that TRPS1 activity is essential to maintain a functional luminal progenitor compartment. This requires the repression of both YAP/TAZ and SRF/MRTF activities. TRPS1 represses SRF/MRTF activity indirectly by modulating RhoA activity. Our work uncovers a hitherto undisclosed function of TRPS1 in luminal progenitors intrinsically linked to mechanotransduction in the mammary gland. It may also provide new insights into the oncogenic functions of TRPS1 as luminal progenitors are likely the cells of origin of many breast cancers.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Breast Cancer ; Luminal Progenitor ; Mammary Gland Homeostasis ; Srf ; Trps1 ; Yap/taz; Breast-cancer; Differentiation; Growth; Cells; Regulator; Complex; Origin; Target; Gata-3; Brca1
ISSN (print) / ISBN
1465-5411
e-ISSN
1465-542X
Journal
Breast Cancer Research
Quellenangaben
Volume: 26,
Issue: 1,
Article Number: 74
Publisher
BioMed Central
Publishing Place
Campus, 4 Crinan St, London N1 9xw, England
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Experimental Genetics (IEG)
Grants
State of Thuringia
Federal Government of Germany
German Cancer Aid (Deutsche Krebshilfe)
DFG
BMBF
Projekt DEAL
Federal Government of Germany
German Cancer Aid (Deutsche Krebshilfe)
DFG
BMBF
Projekt DEAL