The Tumor Suppressor BAP1 Regulates the Hippo Pathway in Pancreatic Ductal Adenocarcinoma.
Journal
Cancer research
ISSN: 1538-7445
Titre abrégé: Cancer Res
Pays: United States
ID NLM: 2984705R
Informations de publication
Date de publication:
15 04 2020
15 04 2020
Historique:
received:
30
05
2019
revised:
04
11
2019
accepted:
17
01
2020
pubmed:
29
1
2020
medline:
9
10
2020
entrez:
29
1
2020
Statut:
ppublish
Résumé
The deubiquitinating enzyme BAP1 is mutated in a hereditary cancer syndrome with a high risk for mesothelioma and melanocytic tumors. Here, we show that pancreatic intraepithelial neoplasia driven by oncogenic mutant KrasG12D progressed to pancreatic adenocarcinoma in the absence of BAP1. The Hippo pathway was deregulated in BAP1-deficient pancreatic tumors, with the tumor suppressor LATS exhibiting enhanced ubiquitin-dependent proteasomal degradation. Therefore, BAP1 may limit tumor progression by stabilizing LATS and thereby promoting activity of the Hippo tumor suppressor pathway. SIGNIFICANCE: BAP1 is mutated in a broad spectrum of tumors. Pancreatic Bap1 deficiency causes acinar atrophy but combines with oncogenic Ras to produce pancreatic tumors. BAP1-deficient tumors exhibit deregulation of the Hippo pathway.
Identifiants
pubmed: 31988076
pii: 0008-5472.CAN-19-1704
doi: 10.1158/0008-5472.CAN-19-1704
doi:
Substances chimiques
BAP1 protein, human
0
Tumor Suppressor Proteins
0
Protein Serine-Threonine Kinases
EC 2.7.11.1
Ubiquitin Thiolesterase
EC 3.4.19.12
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Comment
Langues
eng
Sous-ensembles de citation
IM
Pagination
1656-1668Subventions
Organisme : NCI NIH HHS
ID : R01 CA142873
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA198138
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : CommentOn
Informations de copyright
©2020 American Association for Cancer Research.