Loss of Med1/TRAP220 promotes the invasion and metastasis of human non-small-cell lung cancer cells by modulating the expression of metastasis-related genes

被引:41
作者
Kim, Hyun-Ju [1 ,2 ]
Roh, Mee Sook [3 ]
Son, Choon Hee [4 ]
Kim, Ae Jeong [1 ,2 ]
Jee, Hye Jin [1 ,2 ]
Song, Naree [1 ,2 ]
Kim, Minjee [1 ,2 ]
Seo, Su-Young [5 ]
Yoo, Young Hyun [2 ,6 ]
Yun, Jeanho [1 ,2 ]
机构
[1] Dong A Univ, Coll Med, Dept Biochem, Pusan 602714, South Korea
[2] Dong A Univ, Coll Med, Mitochondria Hub Regulat Ctr, Pusan 602714, South Korea
[3] Dong A Univ, Coll Med, Dept Pathol, Pusan 602714, South Korea
[4] Dong A Univ, Coll Med, Dept Internal Med, Pusan 602714, South Korea
[5] Dong A Univ, Coll Med, Dept Microbiol, Pusan 602714, South Korea
[6] Dong A Univ, Coll Med, Dept Anat & Cell Biol, Pusan 602714, South Korea
基金
新加坡国家研究基金会;
关键词
Non-small-cell lung cancer; Med1; Invasion; Metastasis; Transcription regulation; RECEPTOR-BINDING PROTEIN; NUCLEAR RECEPTORS; PROSTATE-CANCER; BREAST-CANCER; COMPLEX; TRAP220; SUBUNIT; PBP/PPARBP; MIGRATION; ALPHA;
D O I
10.1016/j.canlet.2012.02.009
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Med1/TRAP220 is an essential component of the TRAP/Mediator complex. In this study, we present a novel function of Med1 in human non-small-cell lung cancer (NSCLC) progression. We found that the loss of Med1 expression was strongly associated with increased rates of invasion and metastasis in NSCLC patients. Consistent with lung cancer patient data, the knockdown of Med1 in NSCLC cell lines led to an increase in cell migration and invasion. Med1-depleted cells displayed an increase in metastasis in a xenograft tumor model and in an in vivo metastasis assay. Moreover, a microarray analysis revealed that the mRNA levels of the metastasis-related genes uPAR, ID2, ID4, PTP4A1, PKP3, TGM2, PLD1, TIMP2, RGS2, and HOXA4 were altered upon Med1 knockdown. Collectively, these results suggest that the loss of Med1 increases the invasive potential of human NSCLC cells by modulating the expression of metastasis-related genes. (c) 2012 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:195 / 202
页数:8
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