AMPK beta1 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

Research output: Contribution to journalArticle

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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 beta1 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 beta1 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 beta1 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-1beta (IL1beta), reductions in acetyl-CoA carboxylase (ACC) phosphorylation, and elevated lipogenesis. Collectively, these data indicate that reductions in the AMPK beta1 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.
Original languageEnglish
Pages (from-to)1143-1155
Number of pages13
JournalMolecular Oncology
Volume11
Issue number9
DOIs
Publication statusPublished - Sep 1 2017

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AMP-Activated Protein Kinases
Neoplasms
Lipogenesis
T-Cell Lymphoma
Carcinogenesis
Acetyl-CoA Carboxylase
Protein Subunits
Interleukin-1beta
Protein Isoforms
Phosphorylation
Proteins

Keywords

  • ACC
  • cancer
  • lipogenesis
  • metabolism

Cite this

Houde, V. P., Donzelli, S., Sacconi, A., Galic, S., Hammill, J. A., Bramson, J. L., ... Steinberg, G. R. (2017). AMPK beta1 reduces tumor progression and improves survival in p53 null mice. Molecular Oncology, 11(9), 1143-1155. https://doi.org/10.1002/1878-0261.12079 [doi]

AMPK beta1 reduces tumor progression and improves survival in p53 null mice. / Houde, V. P.; Donzelli, S.; Sacconi, A.; Galic, S.; Hammill, J. A.; Bramson, J. L.; Foster, R. A.; Tsakiridis, T.; Kemp, B. E.; Grasso, G.; Blandino, G.; Muti, P.; Steinberg, G. R.

In: Molecular Oncology, Vol. 11, No. 9, 01.09.2017, p. 1143-1155.

Research output: Contribution to journalArticle

Houde, VP, Donzelli, S, Sacconi, A, Galic, S, Hammill, JA, Bramson, JL, Foster, RA, Tsakiridis, T, Kemp, BE, Grasso, G, Blandino, G, Muti, P & Steinberg, GR 2017, 'AMPK beta1 reduces tumor progression and improves survival in p53 null mice', Molecular Oncology, vol. 11, no. 9, pp. 1143-1155. https://doi.org/10.1002/1878-0261.12079 [doi]
Houde VP, Donzelli S, Sacconi A, Galic S, Hammill JA, Bramson JL et al. AMPK beta1 reduces tumor progression and improves survival in p53 null mice. Molecular Oncology. 2017 Sep 1;11(9):1143-1155. https://doi.org/10.1002/1878-0261.12079 [doi]
Houde, V. P. ; Donzelli, S. ; Sacconi, A. ; Galic, S. ; Hammill, J. A. ; Bramson, J. L. ; Foster, R. A. ; Tsakiridis, T. ; Kemp, B. E. ; Grasso, G. ; Blandino, G. ; Muti, P. ; Steinberg, G. R. / AMPK beta1 reduces tumor progression and improves survival in p53 null mice. In: Molecular Oncology. 2017 ; Vol. 11, No. 9. pp. 1143-1155.
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AB - 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 beta1 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 beta1 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 beta1 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-1beta (IL1beta), reductions in acetyl-CoA carboxylase (ACC) phosphorylation, and elevated lipogenesis. Collectively, these data indicate that reductions in the AMPK beta1 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.

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