Beta-Catenin Causes Adrenal Hyperplasia by Blocking Zonal Transdifferentiation.
Wnt signaling
adrenal cortex
beta-catenin
cell transdifferentiation
hyperplasia
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
21 04 2020
21 04 2020
Historique:
received:
05
09
2019
revised:
16
01
2020
accepted:
26
03
2020
entrez:
23
4
2020
pubmed:
23
4
2020
medline:
15
5
2021
Statut:
ppublish
Résumé
Activating mutations in the canonical Wnt/β-catenin pathway are key drivers of hyperplasia, the gateway for tumor development. In a wide range of tissues, this occurs primarily through enhanced effects on cellular proliferation. Whether additional mechanisms contribute to β-catenin-driven hyperplasia remains unknown. The adrenal cortex is an ideal system in which to explore this question, as it undergoes hyperplasia following somatic β-catenin gain-of-function (βcat-GOF) mutations. Targeting βcat-GOF to zona Glomerulosa (zG) cells leads to a progressive hyperplastic expansion in the absence of increased proliferation. Instead, we find that hyperplasia results from a functional block in the ability of zG cells to transdifferentiate into zona Fasciculata (zF) cells. Mechanistically, zG cells demonstrate an upregulation of Pde2a, an inhibitor of zF-specific cAMP/PKA signaling. Hyperplasia is further exacerbated by trophic factor stimulation leading to organomegaly. Together, these data indicate that β-catenin drives adrenal hyperplasia through both proliferation-dependent and -independent mechanisms.
Identifiants
pubmed: 32320669
pii: S2211-1247(20)30424-1
doi: 10.1016/j.celrep.2020.107524
pmc: PMC7281829
mid: NIHMS1586763
pii:
doi:
Substances chimiques
CTNNB1 protein, mouse
0
beta Catenin
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
107524Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK100653
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK123694
Pays : United States
Organisme : NIDDK NIH HHS
ID : R00 DK100539
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL138241
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK034854
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests E.P., S.L., D.L.C., K.S.B., and D.T.B. declare provisional patent applications US19/38561 and US19/38564 related to this work.
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