Downregulation of Beclin 1 and impairment of autophagy in a small population of colorectal cancer.
Downregulation of Beclin 1 and impairment of autophagy in a small population of colorectal cancer.
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DOI：
10.1007/s10620-013-2732-8
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发表时间：
2013-10
影响因子：
3.1
通讯作者：
Wen, Jifang
中科院分区：
文献类型：
--
作者：
Chen, Zhihong;Li, Yanchun;Zhang, Chi;Yi, Hongmei;Wu, Chang;Wang, Junpu;Liu, Yuwu;Tan, Jieqiong;Wen, Jifang
自噬是一种高度保守的机制，通过降解和回收长寿命蛋白质和受损细胞器来维持细胞内环境的稳定。自噬的失调与肿瘤发生有关。Beclin 1是一种重要的自噬蛋白，在大多数结直肠癌组织中观察到其上调。然而，有一小部分结直肠癌患者Beclin 1表达下调。本研究的目的是研究自噬在Beclin 1下调的结直肠癌中的作用。采用ICH和WB检测结直肠癌组织中自噬体标志物LC 3蛋白的表达。通过在体外引入外源Beclin 1来检查Beclin 1的抗肿瘤效果。分析集落形成试验、生长曲线和小鼠异种移植物。我们的结果显示，LC 3在结直肠癌中被抑制（9.86%），Beclin 1下调。此外，Beclin 1的过表达抑制结直肠癌细胞的生长，并增强雷帕霉素诱导的体外抗肿瘤作用。Beclin 1表达下调和自噬抑制在部分结直肠癌中发挥重要作用。激活Beclin 1的自噬或过表达可能是某些结直肠癌的有效治疗方法。检测Beclin 1在结直肠癌中的表达谱可能为结直肠癌的诊断和治疗提供新的策略。本文的在线版本（doi：10.1007/s10620-013-2732-8）包含补充材料，可供授权用户使用。
Autophagy is a highly conserved mechanism for degradation and recycling of long-lived proteins and damaged organelle to maintain cell homeostasis. Deregulation of autophagy has been associated with tumorigenesis. Beclin 1 is an essential autophagy protein and its upregulation has been observed in most colorectal cancer tissues. However, there is a small population of colorectal cancers with downregulation of Beclin 1. The purpose of this study was to investigate the role autophagy plays in colorectal cancers with downregulaion of Beclin 1. LC3 protein, an autophagosome marker, was assessed by ICH and WB in colorectal cancers tissues. An anti-tumor effect of Beclin 1 was examined by introducing exogenous Beclin 1 in vitro. Colony formation assay, growth curves and mouse xenograft were analysed. Our results showed that LC3 was suppressed in the colorectal cancers (9.86 %) with downregulation of Beclin 1. Moreover, overexpression of Beclin 1 inhibited colorectal cancer cell growth and enhanced the rapamycin-induced antitumor effect in vitro. Downregulation of Beclin 1 and autophagy inhibition play an important role in a part of colorectal cancers. Activating autophagy or overexperssion of Beclin 1 may be an effective treatment for some colorectal cancers. Detection of expression profile of Beclin 1 in colorectal cancers could be a strategy for new diagnostic and therapeutic methods. The online version of this article (doi:10.1007/s10620-013-2732-8) contains supplementary material, which is available to authorized users.
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影响因子：
64.5
作者：
Liu J;Xia H;Kim M;Xu L;Li Y;Zhang L;Cai Y;Norberg HV;Zhang T;Furuya T;Jin M;Zhu Z;Wang H;Yu J;Li Y;Hao Y;Choi A;Ke H;Ma D;Yuan J
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Yuan J
DOI：
10.1016/j.biocel.2013.02.007
发表时间：
2013-05-01
影响因子：
4
作者：
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通讯作者：
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影响因子：
78.5
作者：
Mathew, Robin;Karantza-Wadsworth, Vassiliki;White, Eileen
通讯作者：
White, Eileen
DOI：
10.1073/pnas.87.19.7555
发表时间：
1990-10-01
影响因子：
11.1
作者：
RODRIGUES, NR;ROWAN, A;LANE, DP
通讯作者：
LANE, DP
影响因子：
2.8
作者：
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通讯作者：
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