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.
AMPK β1 reduces tumor progression and improves survival in p53 null mice / V.P. Houde, S. Donzelli, A. Sacconi, S. Galic, J.A. Hammill, J.L. Bramson, R.A. Foster, T. Tsakiridis, B.E. Kemp, G. Grasso, G. Blandino, P. Muti, G.R. Steinberg. - In: MOLECULAR ONCOLOGY. - ISSN 1574-7891. - 11:9(2017), pp. 1143-1155.
|Titolo:||AMPK β1 reduces tumor progression and improves survival in p53 null mice|
|Parole Chiave:||ACC; cancer; lipogenesis; metabolism; AMP-Activated Protein Kinases; Acetyl-CoA Carboxylase; Animals; Gene Deletion; Lipogenesis; Lymphoma, T-Cell; Mice, Inbred C57BL; Phosphorylation; Survival Analysis; Tumor Suppressor Protein p53; Disease Progression|
|Settore Scientifico Disciplinare:||Settore MED/13 - Endocrinologia|
|Data di pubblicazione:||2017|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1002/1878-0261.12079|
|Appare nelle tipologie:||01 - Articolo su periodico|