p62 degradation by autophagy Another way for cancer cells to survive under hypoxia
p62 degradation by autophagy Another way for cancer cells to survive under hypoxia
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DOI：
10.4161/auto.5.3.7823
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发表时间：
2009-04-01
期刊：
影响因子：
13.3
通讯作者：
Pursiheimo, Juha-Pekka
中科院分区：
文献类型：
--
作者：
Jaakkola, Panu M.;Pursiheimo, Juha-Pekka
缺氧是晚期实体瘤导致癌症进展和治疗抵抗的共同特征。缺氧激活线粒体自噬和巨噬，调节癌细胞存活。p62/SQSTM1是一种多功能蛋白，其目标是蛋白酶体和自噬降解的蛋白，它本身在缺氧激活的癌细胞自噬中被下调。p62的缺氧降解在几种癌细胞系中可见。与缺氧激活线粒体自噬相反，缺氧诱导的p62降解部分独立于HIF途径发生。这一发现表明，除了通过HIF进行转录基因调控外，自噬在缺氧癌细胞存活反应的调控中也起着核心作用。
Hypoxia is a common feature of advanced solid tumors causing cancer progression and resistance to treatment. Hypoxia activates mitophagy as well as macroautophagy that regulates carcinoma cell survival. p62/SQSTM1, a multifunctional protein that targets proteins to degradation by proteasomes and autophagy, is itself downregulated by hypoxia-activated autophagy in carcinoma cells. The hypoxic degradation of p62 is seen across several carcinoma cell lines. In contrast to hypoxic activation of mitochondrial autophagy, the hypoxia-induced degradation of p62 occurs partially independently from the HIF pathway. The finding argues that in addition to transcriptional gene regulation through HIF, autophagy has a central role in the regulation of hypoxic cancer cell survival responses.