AMPK β1 reduces tumor progression and improves survival in p53 null mice.
AMPK β1 reduces tumor progression and improves survival in p53 null mice.
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DOI：
10.1002/1878-0261.12079
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发表时间：
2017-09
影响因子：
6.6
通讯作者：
Steinberg GR
中科院分区：
文献类型：
--
作者：
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
AMP活化蛋白激酶（AMPK）是一种异源三聚体蛋白复合物，是细胞能量状态的重要传感器。AMPK β1亚型的表达减少与不同癌症的生存率降低有关，但这是否会加速肿瘤进展以及介导这些效应的潜在机制尚不清楚。此外，目前还不清楚AMPK β1是否与肿瘤发生有关，如果是，哪些组织可能最敏感。在目前的研究中，我们发现在没有肿瘤抑制因子p53的情况下，AMPK β1的生殖系遗传缺失加速了T细胞淋巴瘤的出现，与单独的p53缺陷相比，T细胞淋巴瘤缩短了寿命。这种增加的肿瘤发生与白细胞介素-1 β（IL 1 β）的增加、乙酰辅酶A羧化酶（ACC）磷酸化的减少和脂肪生成的增加有关。总的来说，这些数据表明AMPK β1亚基的减少加速了T细胞淋巴瘤的发展，这表明靶向AMPK亚基或抑制脂肪生成的疗法可能有效限制p53突变型肿瘤的增殖。
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.
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DOI：
10.1126/science.1215327
发表时间：
2012-05-18
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hawley SA;Fullerton MD;Ross FA;Schertzer JD;Chevtzoff C;Walker KJ;Peggie MW;Zibrova D;Green KA;Mustard KJ;Kemp BE;Sakamoto K;Steinberg GR;Hardie DG
通讯作者：
Hardie DG
DOI：
10.1158/1055-9965.epi-12-1014
发表时间：
2013-04
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子：
--
作者：
Hoffman AE;Demanelis K;Fu A;Zheng T;Zhu Y
通讯作者：
Zhu Y
影响因子：
64.8
作者：
DONEHOWER, LA;HARVEY, M;BRADLEY, A
通讯作者：
BRADLEY, A
影响因子：
12.4
作者：
Adamovich, Y.;Adler, J.;Shaul, Y.
通讯作者：
Shaul, Y.
影响因子：
3.5
作者：
Foretz, Marc;Guihard, Soizic;Viollet, Benoit
通讯作者：
Viollet, Benoit