c-Crk proto-oncogene contributes to transcriptional repression of p120-catenin in non-small cell lung cancer cells.
c-Crk proto-oncogene contributes to transcriptional repression of p120-catenin in non-small cell lung cancer cells.
复制标题
DOI：
10.1007/s10585-011-9378-8
复制
发表时间：
2011-04
影响因子：
4
通讯作者：
Rettig, Matthew
中科院分区：
文献类型：
--
作者：
Mortazavi, Fariborz;Dubinett, Steven;Rettig, Matthew
p120-catenin （p120ctn）作为粘附连接的成员，通过稳定E-cadherin在细胞粘附中发挥重要作用。p120ctn在非小细胞肺癌（NSCLC）中转录下调，尽管p120ctn抑制的分子机制尚不完全明确。在这里，我们进一步研究了p120ctn在非小细胞肺癌中的转录调控。我们制备了一个包含p120ctn启动子区域的启动子报告质粒，该启动子区域相对于转录起始位点的位置为−1082至+320。通过p120ctn启动子的序列缺失突变分析，我们确定了参与p120ctn调控的顺式作用元件。我们发现转录因子SP1是p120ctn的转录抑制因子，它直接结合p120ctn启动子的- 9到+36段。SP1可以接受来自多种细胞内信号通路的多种信号。通过SP1结合伴侣的检测，我们发现原癌基因c-Crk参与了p120ctn的转录下调。RNAi介导的CRK沉默在A549、H157和H358细胞中增加了p120ctn蛋白水平。另一方面，NSCLC细胞中CRK-I和CRK-II的过表达下调了p120ctn，而SP1的同时沉默则消除了这一作用。总之，我们的数据为c-Crk原癌基因在p120ctn转录抑制中的作用提供了证据，进一步阐明了该生化信号促进非小细胞肺癌转移的机制。本文的在线版本（doi:10.1007/s10585-011-9378-8）包含补充材料，仅供授权用户使用。
As a member of adherens junction, p120-catenin (p120ctn) plays a major role in cell adhesions through stabilization of E-cadherin. p120ctn is transcriptionally down-regulated in non-small cell lung cancer (NSCLC), although the molecular mechanisms underlying p120ctn repression are incompletely defined. Here we further investigated transcriptional regulation of p120ctn in NSCLC. We prepared a promoter reporter plasmid construct that contained p120ctn promoter region from position −1082 to +320 relative to transcription start site. Through serial deletion mutation analysis of the p120ctn promoter, we pinpointed cis-acting elements involved in regulation of p120ctn. We identified transcription factor SP1 as a transcriptional repressor of p120ctn that directly binds to segment (−9 to +36) of the p120ctn promoter. SP1 can receive multiple signals from several intracellular signaling pathways. Through examination of SP1 binding partners, we identified proto-oncogene c-Crk to be involved in transcriptional down-regulation of p120ctn. RNAi mediated silencing of CRK in A549, H157 and H358 cells increased p120ctn protein levels. On the other hand, over-expression of CRK-I and CRK-II in NSCLC cells down-regulated p120ctn, an effect that was abrogated by simultaneous silencing of SP1. In summary, our data provide evidence for the role of c-Crk proto-oncogene in transcriptional repression of p120ctn that further clarifies the mechanism by which this biochemical signal promotes metastasis in NSCLC. The online version of this article (doi:10.1007/s10585-011-9378-8) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
21.3
作者：
Reddien, PW;Horvitz, HR
通讯作者：
Horvitz, HR
p120ctn 亚型 1 和 3 的减少与人类肺癌的转移进展显着相关
影响因子：
2.8
作者：
Liu, Yang;Xu, Hong-Tao;Wang, En-Hua
通讯作者：
Wang, En-Hua
影响因子：
4.3
作者：
Zhai, Bo;Yan, He-Xin;Wang, Hong-Yang
通讯作者：
Wang, Hong-Yang
P120-catenin亚型1A和3A对肺癌细胞侵袭和增殖的影响不同
影响因子：
3.7
作者：
Liu, Yang;Dong, Qian-Ze;Wang, En-Hua
通讯作者：
Wang, En-Hua
影响因子：
4
作者：
Kelly, KF;Spring, CM;Daniel, JM
通讯作者：
Daniel, JM