Ontology type: schema:ScholarlyArticle Open Access: True
2016-09-14
AUTHORSCoralie Drelon, Annabel Berthon, Isabelle Sahut-Barnola, Mickaël Mathieu, Typhanie Dumontet, Stéphanie Rodriguez, Marie Batisse-Lignier, Houda Tabbal, Igor Tauveron, Anne-Marie Lefrançois-Martinez, Jean-Christophe Pointud, Celso E Gomez-Sanchez, Seppo Vainio, Jingdong Shan, Sonia Sacco, Andreas Schedl, Constantine A Stratakis, Antoine Martinez, Pierre Val
ABSTRACTAdrenal cortex physiology relies on functional zonation, essential for production of aldosterone by outer zona glomerulosa (ZG) and glucocorticoids by inner zona fasciculata (ZF). The cortex undergoes constant cell renewal, involving recruitment of subcapsular progenitors to ZG fate and subsequent lineage conversion to ZF identity. Here we show that WNT4 is an important driver of WNT pathway activation and subsequent ZG differentiation and demonstrate that PKA activation prevents ZG differentiation through WNT4 repression and WNT pathway inhibition. This suggests that PKA activation in ZF is a key driver of WNT inhibition and lineage conversion. Furthermore, we provide evidence that constitutive PKA activation inhibits, whereas partial inactivation of PKA catalytic activity stimulates β-catenin-induced tumorigenesis. Together, both lower PKA activity and higher WNT pathway activity lead to poorer prognosis in adrenocortical carcinoma (ACC) patients. These observations suggest that PKA acts as a tumour suppressor in the adrenal cortex, through repression of WNT signalling. More... »
PAGES12751
http://scigraph.springernature.com/pub.10.1038/ncomms12751
DOIhttp://dx.doi.org/10.1038/ncomms12751
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PUBMEDhttps://www.ncbi.nlm.nih.gov/pubmed/27624192
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