Autophagy defects suggested by low levels of autophagy activator MAP1S and high levels of autophagy inhibitor LRPPRC predict poor prognosis of prostate cancer patients.
Autophagy defects suggested by low levels of autophagy activator MAP1S and high levels of autophagy inhibitor LRPPRC predict poor prognosis of prostate cancer patients.
复制标题
低水平的自噬激活剂 MAP1S 和高水平的自噬抑制剂 LRPPRC 提示的自噬缺陷预示着前列腺癌患者的不良预后。
DOI：
10.1002/mc.22193
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发表时间：
2015-10
影响因子：
4.6
通讯作者：
Liu L
中科院分区：
文献类型：
--
作者：
Jiang X;Zhong W;Huang H;He H;Jiang F;Chen Y;Yue F;Zou J;Li X;He Y;You P;Yang W;Lai Y;Wang F;Liu L
MAP1S(最初命名为C19ORF5)是神经元特异性MAP1A和MAP1B的广泛分布的同系物，它将自噬成分与微管和线粒体连接起来，影响自噬的生物发生和降解。线粒体相关蛋白LRPPRC作为自噬启动的抑制因子，保护线粒体免受自噬降解。MAP1S和LRPPRC相互作用，可能协同调节自噬，尽管潜在的机制尚不清楚。此前，我们曾报道LRPPRC水平可作为前列腺癌(PCA)患者的预后标志物，LRPPRC水平高的患者术后生存期短于LRPPRC水平低的患者。在二乙基亚硝胺诱导的野生型小鼠肝细胞癌中，MAP1S水平升高，暴露于MAP1S缺陷的小鼠患上更多的恶性肝细胞癌。我们进行了免疫化学分析，以评估MAP1S、LRPPRC、p62和γ-H2AX水平之间的相互关系。样本来自野生型和前列腺特异性PTEN基因缺陷小鼠，经10年随访的前列腺癌患者111例和广州医院收治的良性前列腺增生症患者38例，中国。MAP1S的水平普遍升高，因此在PTEN缺陷小鼠或患者的PCa中，MAP1S介导的自噬被激活，而不是各自的良性肿瘤。前列腺癌患者的MAP1S水平差异很大，MAP1S水平低的患者生存时间比MAP1S水平高的患者短。MAP1S水平和LRPPRC水平可作为前列腺癌患者预后的标志物。
MAP1S (originally named C19ORF5) is a widely distributed homolog of neuronal-specific MAP1A and MAP1B, and bridges autophagic components with microtubules and mitochondria to affect autophagosomal biogenesis and degradation. Mitochondrion-associated protein LRPPRC functions as an inhibitor for autophagy initiation to protect mitochondria from autophagy degradation. MAP1S and LRPPRC interact with each other and may collaboratively regulate autophagy although the underlying mechanism is yet unknown. Previously, we have reported that LRPPRC levels serve as a prognosis marker of patients with prostate adenocarcinomas (PCA), and that patients with high LRPPRC levels survive a shorter period after surgery than those with low levels of LRPPRC. MAP1S levels are elevated in diethylnitrosamine-induced hepatocelular carcinomas in wildtype mice and the exposed MAP1S-deficient mice develop more malignant hepatocellular carcinomas. We performed immunochemical analysis to evaluate the co-relationship among the levels of MAP1S, LRPPRC, P62, and γ-H2AX. Samples were collected from wildtype and prostate-specific PTEN-deficient mice, 111 patients with PCA who had been followed up for 10 years and 38 patients with benign prostate hyperplasia enrolled in hospitals in Guangzhou, China. The levels of MAP1S were generally elevated so the MAP1S-mediated autophagy was activated in PCA developed in either PTEN-deficient mice or patients than their respective benign tumors. The MAP1S levels among patients with PCA vary dramatically, and patients with low MAP1S levels survive a shorter period than those with high MAP1S levels. Levels of MAP1S in collaboration with levels of LRPPRC can serve as markers for prognosis of prostate cancer patients.