AMPK β1 reduces tumor progression and improves survival in p53 null mice
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 mech...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2017-09-01
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| Series: | Molecular Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/1878-0261.12079 |
| _version_ | 1828118423152885760 |
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| author | Vanessa P. Houde Sara Donzelli Andrea Sacconi Sandra Galic Joanne A. Hammill Jonathan L. Bramson Robert A. Foster Theodoros Tsakiridis Bruce E. Kemp Giuseppe Grasso Giovanni Blandino Paola Muti Gregory R. Steinberg |
| author_facet | Vanessa P. Houde Sara Donzelli Andrea Sacconi Sandra Galic Joanne A. Hammill Jonathan L. Bramson Robert A. Foster Theodoros Tsakiridis Bruce E. Kemp Giuseppe Grasso Giovanni Blandino Paola Muti Gregory R. Steinberg |
| author_sort | Vanessa P. Houde |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T13:31:54Z |
| format | Article |
| id | doaj.art-2f7ed24678f9476889ae039ad8531ce5 |
| institution | Directory Open Access Journal |
| issn | 1574-7891 1878-0261 |
| language | English |
| last_indexed | 2024-04-11T13:31:54Z |
| publishDate | 2017-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Oncology |
| spelling | doaj.art-2f7ed24678f9476889ae039ad8531ce52022-12-22T04:21:47ZengWileyMolecular Oncology1574-78911878-02612017-09-011191143115510.1002/1878-0261.12079AMPK β1 reduces tumor progression and improves survival in p53 null miceVanessa P. Houde0Sara Donzelli1Andrea Sacconi2Sandra Galic3Joanne A. Hammill4Jonathan L. Bramson5Robert A. Foster6Theodoros Tsakiridis7Bruce E. Kemp8Giuseppe Grasso9Giovanni Blandino10Paola Muti11Gregory R. Steinberg12Department of Oncology McMaster University Hamilton CanadaOncogenomic and Epigenetic Unit Italian National Cancer Institute ‘Regina Elena’ Rome ItalyOncogenomic and Epigenetic Unit Italian National Cancer Institute ‘Regina Elena’ Rome ItalySt. Vincent's Institute of Medical Research and Department of Medicine University of Melbourne AustraliaDepartment of Pathology and Molecular Medicine McMaster University Hamilton CanadaDepartment of Pathology and Molecular Medicine McMaster University Hamilton CanadaDepartment of Pathobiology Ontario Veterinary College University of Guelph CanadaDepartment of Oncology McMaster University Hamilton CanadaSt. Vincent's Institute of Medical Research and Department of Medicine University of Melbourne AustraliaOncogenomic and Epigenetic Unit Italian National Cancer Institute ‘Regina Elena’ Rome ItalyDepartment of Oncology McMaster University Hamilton CanadaDepartment of Oncology McMaster University Hamilton CanadaDepartment of Medicine McMaster University Hamilton CanadaThe 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.https://doi.org/10.1002/1878-0261.12079ACCmetabolismcancerlipogenesis |
| spellingShingle | Vanessa P. Houde Sara Donzelli Andrea Sacconi Sandra Galic Joanne A. Hammill Jonathan L. Bramson Robert A. Foster Theodoros Tsakiridis Bruce E. Kemp Giuseppe Grasso Giovanni Blandino Paola Muti Gregory R. Steinberg AMPK β1 reduces tumor progression and improves survival in p53 null mice Molecular Oncology ACC metabolism cancer lipogenesis |
| title | AMPK β1 reduces tumor progression and improves survival in p53 null mice |
| title_full | AMPK β1 reduces tumor progression and improves survival in p53 null mice |
| title_fullStr | AMPK β1 reduces tumor progression and improves survival in p53 null mice |
| title_full_unstemmed | AMPK β1 reduces tumor progression and improves survival in p53 null mice |
| title_short | AMPK β1 reduces tumor progression and improves survival in p53 null mice |
| title_sort | ampk β1 reduces tumor progression and improves survival in p53 null mice |
| topic | ACC metabolism cancer lipogenesis |
| url | https://doi.org/10.1002/1878-0261.12079 |
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