Oncogene-Induced Senescence Limits the Progression of Pancreatic Neoplasia through Production of Activin A.
Activin Receptors, Type I
/ genetics
Activin Receptors, Type II
/ metabolism
Activins
/ antagonists & inhibitors
Animals
Carcinoma, Pancreatic Ductal
/ etiology
Cellular Senescence
/ physiology
Disease Progression
Genes, ras
Humans
Mice
Pancreatic Neoplasms
/ etiology
Phosphorylation
Precancerous Conditions
/ etiology
Proto-Oncogene Proteins p21(ras)
/ metabolism
Transcriptional Activation
Journal
Cancer research
ISSN: 1538-7445
Titre abrégé: Cancer Res
Pays: United States
ID NLM: 2984705R
Informations de publication
Date de publication:
15 08 2020
15 08 2020
Historique:
received:
19
12
2019
revised:
08
04
2020
accepted:
12
06
2020
pubmed:
20
6
2020
medline:
29
12
2020
entrez:
20
6
2020
Statut:
ppublish
Résumé
Pancreatic ductal adenocarcinoma (PDAC) is a deadly and aggressive cancer. Understanding mechanisms that drive preneoplastic pancreatic lesions is necessary to improve early diagnostic and therapeutic strategies. Mutations and inactivation of activin-like kinase (ALK4) have been demonstrated to favor PDAC onset. Surprisingly, little is known regarding the ligands that drive ALK4 signaling in pancreatic cancer or how this signaling pathway limits the initiation of neoplastic lesions. In this study, data mining and histologic analyses performed on human and mouse tumor tissues revealed that activin A is the major ALK4 ligand that drives PDAC initiation. Activin A, which is absent in normal acinar cells, was strongly induced during acinar-to-ductal metaplasia (ADM), which was promoted by pancreatitis or the activation of Kras
Identifiants
pubmed: 32554750
pii: 0008-5472.CAN-19-3763
doi: 10.1158/0008-5472.CAN-19-3763
doi:
Substances chimiques
activin A
0
Activins
104625-48-1
Activin Receptors, Type I
EC 2.7.11.30
Activin Receptors, Type II
EC 2.7.11.30
Proto-Oncogene Proteins p21(ras)
EC 3.6.5.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3359-3371Informations de copyright
©2020 American Association for Cancer Research.