The subcellular distribution and function of MTA1 in cancer differentiation.

The subcellular distribution and function of MTA1 in cancer differentiation.
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MTA1在癌症分化中的亚细胞分布和功能

DOI:
10.18632/oncotarget.2095
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发表时间:
2014-07-15
期刊:
影响因子:
--
通讯作者:
Qian H
Qian H
中科院分区:
其他
文献类型:
--
作者:
Liu J;Xu D;Wang H;Zhang Y;Chang Y;Zhang J;Wang J;Li C;Liu H;Zhao M;Lin C;Zhan Q;Huang C;Qian H

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由于对转移相关蛋白1(metastasis-associated protein 1,MTA 1)亚细胞定位的认识相对滞后,MTA 1在肿瘤进展中的作用和机制尚不清楚。在本研究中,利用多种分子技术,我们首次证实了MTA 1定位于细胞核,细胞质和核膜。MTA 1主要定位于正常成人组织的细胞核中,但在胚胎组织的细胞质中。而在结肠癌中,两种分布都有描述。进一步的研究表明,MTA 1定位在核膜上的易位启动子区(TPR)依赖的方式,而在细胞质中,MTA 1显示出明显的微管定位。细胞核和细胞质MTA 1都与癌症进展相关。然而,这些功能可能与不同的机制有关,因为只有核MTA 1与癌症分化有关。在HCT 116细胞中,过表达MTA 1抑制分化并促进增殖,而MTA 1敲低导致细胞分化和死亡。这些结果不仅表明,核MTA 1是一个很好的肿瘤鉴别诊断的标志物和潜在的治疗癌症的目标,但也揭示了区分核和胞质MTA 1的功能的必要性。
The functions and mechanisms of metastasis-associated protein 1 (MTA1) in cancer progression are still unclear due to a lagged recognition of the subcellular localization. In the present study, using multiple molecular technologies we confirmed for the first time that MTA1 localizes to the nucleus, cytoplasm and nuclear envelope. MTA1 is primarily localized in the nucleus of normal adult tissues but in the cytoplasm of embryonic tissues. While in colon cancer, both distributions have been described. Further investigation revealed that MTA1 localizes on the nuclear envelope in a translocated promoter region (TPR)-dependent manner, while in the cytoplasm, MTA1 shows an obvious localization on microtubules. Both nuclear and cytoplasmic MTA1 are associated with cancer progression. However, these functions may be associated with different mechanisms because only nuclear MTA1 has been associated with cancer differentiation. Overexpression of MTA1 in HCT116 cells inhibited differentiation and promoted proliferation, whereas MTA1 knockdown resulted in cell differentiation and death. Theses results not only suggest that nuclear MTA1 is a good marker for cancer differentiation diagnosis and a potential target for the treatment of cancers but also reveal the necessity to differentially examine the functions of nuclear and cytoplasmic MTA1.
DOI: 10.1016/j.humpath.2006.01.024
发表时间: 2006-06-01
期刊: HUMAN PATHOLOGY
影响因子: 3.3
作者:
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期刊: MOLECULAR CELL
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发表时间: 2007-08-01
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DOI: 10.1083/jcb.141.1.31
发表时间: 1998-04-06
期刊: The Journal of cell biology
影响因子: --
作者:
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DOI: 10.1074/mcp.m700166-mcp200
发表时间: 2007-09-01
影响因子: 7
作者:
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