Down-regulation of tumor endothelial marker 8 suppresses cell proliferation mediated by ERK1/2 activity.

Down-regulation of tumor endothelial marker 8 suppresses cell proliferation mediated by ERK1/2 activity.
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肿瘤内皮标志物 8 的下调可抑制 ERK1/2 活性介导的细胞增殖。

DOI:
10.1038/srep23419
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发表时间:
2016-03-21
期刊:
影响因子:
4.6
通讯作者:
Wang L
Wang L
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Cao C;Wang Z;Huang L;Bai L;Wang Y;Liang Y;Dou C;Wang L

文献摘要

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肿瘤内皮标志物8(tumor endothelial marker 8,TEM 8)在肿瘤细胞和正常内皮细胞中的选择性过表达被认为是多种肿瘤的抗肿瘤靶点。本研究旨在探讨TEM 8在骨肉瘤中的作用。总体而言,TEM 8主要位于细胞质中,并且与良性骨病变和邻近非肿瘤组织(ANT)相比,在骨肉瘤中上调。TEM 8高表达组总生存率明显低于TEM 8低表达组。通过siRNA或shRNA敲低TEM 8导致骨肉瘤细胞在体外和体内的生长和增殖显著减少。TEM 8的阻断导致Erk 1/2介导的p21和p27的表达增加和cyclin D1的抑制。提示TEM 8的下调在抑制骨肉瘤的发生发展中起重要作用。
Tumor endothelial marker 8 (TEM8) was recently suggested as a putative anti-tumor target in several types of human cancer based on its selective overexpression in tumor versus normal endothelial cells. The objective of this study was to detect the potential functions of TEM8 in osteosarcoma. Overall, TEM8 was mainly located in cytoplasm and was up-regulated in osteosarcoma compared to benign bone lesions and adjacent non tumor tissue (ANT). High TEM8 expression group had a significant lower overall survival rate than that in the low TEM8 expression group. TEM8 knock-down by siRNA or shRNA results in significant reduction of osteosarcoma cell growth and proliferation both in vitro and in vivo. Ablation of TEM8 led to increasing of p21 and p27 and suppression of cyclin D1 mediated by Erk1/2 activity. These findings suggest that down-regulation of TEM8 play an important role in the inhibition of tumorigenesis and development of osteosarcoma.