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
    
 
    
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        Keywords
        Breast Cancer ; Luminal Progenitor ; Mammary Gland Homeostasis ; Srf ; Trps1 ; Yap/taz; Breast-cancer; Differentiation; Growth; Cells; Regulator; Complex; Origin; Target; Gata-3; Brca1
    
 
    
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        Language
        english
    
 
    
        Publication Year
        2024
    
 
    
        Prepublished in Year
        0
    
 
    
        HGF-reported in Year
        2024
    
 
    
    
        ISSN (print) / ISBN
        1465-5411
    
 
    
        e-ISSN
        1465-542X
    
 
    
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	    Volume: 26,  
	    Issue: 1,  
	    Pages: ,  
	    Article Number: 74 
	    Supplement: ,  
	
    
 
    
        
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            Publisher
            BioMed Central
        
 
        
            Publishing Place
            Campus, 4 Crinan St, London N1 9xw, England
        
 
	
        
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        Reviewing status
        Peer reviewed
    
 
     
    
        POF-Topic(s)
        30201 - Metabolic Health
    
 
    
        Research field(s)
        Genetics and Epidemiology
    
 
    
        PSP Element(s)
        G-500692-001
G-500600-001
    
 
    
        Grants
        State of Thuringia
Federal Government of Germany
German Cancer Aid (Deutsche Krebshilfe)
DFG
BMBF
Projekt DEAL
    
 
    
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        Erfassungsdatum
        2024-05-21