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AMPK ß1 reduces tumor progression and improves survival in p53 null mice
Houde, Vanessa P. Donzelli, Sara Sacconi, Andrea Galic, Sandra Hammill, Joanne A. Bramson, Jonathan L. Foster, Robert A. Tsakiridis, Theodoros Kemp, Bruce Grasso, Giuseppe
Houde, Vanessa P.
Donzelli, Sara
Sacconi, Andrea
Galic, Sandra
Hammill, Joanne A.
Bramson, Jonathan L.
Foster, Robert A.
Tsakiridis, Theodoros
Kemp, Bruce
Grasso, Giuseppe
Abstract
The AMP‐activated protein kinase (AMPK) is a heterotrimeric protein complex that is an important sensor of cellular energy status. Reduced expression of the AMPK β1 isoform has been linked to reduced survival in different cancers, but whether this accelerates tumor progression and the potential mechanism mediating these effects are not known. Furthermore, it is unknown whether AMPK β1 is implicated in tumorigenesis, and if so, what tissues may be most sensitive. In the current study, we find that in the absence of the tumor suppressor p53, germline genetic deletion of AMPK β1 accelerates the appearance of a T‐cell lymphoma that reduces lifespan compared to p53 deficiency alone. This increased tumorigenesis is linked to increases in interleukin‐1β (IL1β), reductions in acetyl‐CoA carboxylase (ACC) phosphorylation, and elevated lipogenesis. Collectively, these data indicate that reductions in the AMPK β1 subunit accelerate the development of T‐cell lymphoma, suggesting that therapies targeting this AMPK subunit or inhibiting lipogenesis may be effective for limiting the proliferation of p53‐mutant tumors.
Keywords
Date
2017
Type
Journal article
Journal
Molecular Oncology
Book
Volume
11
Issue
9
Page Range
1143-1155
Article Number
ACU Department
Faculty of Health Sciences
Collections
Relation URI
Source URL
Event URL
Open Access Status
Open access
License
CC BY 4.0
File Access
Open