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Tollot-Wegner, M.* ; Jessen, M.* ; Kim, K.* ; Sanz-Moreno, A. ; Spielmann, N. ; Gailus-Durner, V. ; Fuchs, H. ; Hrabě de Angelis, M. ; von Eyss, B.*

TRPS1 maintains luminal progenitors in the mammary gland by repressing SRF/MRTF activity.

Breast Cancer Res. 26:74 (2024)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter 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
Zeitschrift Breast Cancer Research
Quellenangaben Band: 26, Heft: 1, Seiten: , Artikelnummer: 74 Supplement: ,
Verlag BioMed Central
Verlagsort Campus, 4 Crinan St, London N1 9xw, England
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Experimental Genetics (IEG)
Förderungen State of Thuringia
Federal Government of Germany
German Cancer Aid (Deutsche Krebshilfe)
DFG
BMBF
Projekt DEAL