AMPK-mediated autophagy is a survival mechanism in androgen-dependent prostate cancer cells subjected to androgen deprivation and hypoxia.
AMPK-mediated autophagy is a survival mechanism in androgen-dependent prostate cancer cells subjected to androgen deprivation and hypoxia.
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DOI：
10.1016/j.cellsig.2011.04.008
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发表时间：
2011-09
影响因子：
4.8
通讯作者：
Ip C
中科院分区：
文献类型：
--
作者：
Chhipa RR;Wu Y;Ip C
本研究旨在研究(i) AMPK激活在雄激素依赖性前列腺癌细胞在雄激素剥夺和缺氧条件下诱导自噬的作用，以及（ii）自噬是否在这些恶劣条件下提供生存优势。低雄激素和低氧是手术或药物阉割后前列腺癌组织中常见的两种共存状况。在LNCaP细胞中，雄激素剥夺和缺氧共同促进AMPK激活到比单独使用任何一种情况更高的水平。AMPK反应的增强与细胞活力的提高和自噬的诱导有关。这些观察结果表明，为了触发自噬，AMPK活性必须达到一个阈值，因为雄激素剥夺或缺氧本身都无法使AMPK活性超过该阈值。Beclin-1被认为是AMPK开启自噬级联的潜在下游靶点。如果通过化学抑制或关键调节因子如AMPK或beclin-1的RNA干扰来阻断自噬，更多的细胞会因凋亡而死亡。因此，自噬的发生是雄激素依赖性前列腺癌细胞摆脱雄激素缺乏和缺氧生存的一种生存机制。
The present study was designed to investigate (i) the role of AMPK activation in inducing autophagy in androgen-dependent prostate cancer cells subjected to androgen deprivation and hypoxia, and (ii) whether autophagy offers a survival advantage under these harsh conditions. Low androgen and low oxygen are two co-existing conditions frequently found in prostate cancer tissue following surgical or medical castration. In LNCaP cells, androgen deprivation and hypoxia together boosted AMPK activation to a higher level than that seen with either condition alone. The augmented AMPK response was associated with improved viability and the induction of autophagy. These observations suggest that a threshold of AMPK activity has to be attained in order to trigger autophagy, since neither androgen deprivation nor hypoxia by itself was capable of pushing AMPK activity past that threshold. Beclin-1 was identified as a potential downstream target of AMPK in turning on the autophagic cascade. If autophagy was blocked by chemical inhibition or RNA interference of key regulators, e.g., AMPK or beclin-1, more cells would die by apoptosis. The occurrence of autophagy is thus a survival mechanism for androgen-dependent prostate cancer cells to escape from an androgen-deprived and hypoxic subsistence.
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影响因子：
29
作者：
Zhao M;Klionsky DJ
通讯作者：
Klionsky DJ
AMP激活的蛋白激酶对ULK1（HATG1）的磷酸化将能量传感连接到线粒体。
DOI：
10.1126/science.1196371
发表时间：
2011-01-28
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Egan DF;Shackelford DB;Mihaylova MM;Gelino S;Kohnz RA;Mair W;Vasquez DS;Joshi A;Gwinn DM;Taylor R;Asara JM;Fitzpatrick J;Dillin A;Viollet B;Kundu M;Hansen M;Shaw RJ
通讯作者：
Shaw RJ
DOI：
10.1016/j.bbrc.2004.06.133
发表时间：
2004-08-11
影响因子：
3.1
作者：
Xiang, XQ;Saha, AK;Luo, ZJ
通讯作者：
Luo, ZJ
影响因子：
78.5
作者：
Mathew, Robin;Karantza-Wadsworth, Vassiliki;White, Eileen
通讯作者：
White, Eileen
影响因子：
12.4
作者：
Katayama, M.;Kawaguchi, T.;Pieper, R. O.
通讯作者：
Pieper, R. O.