SIX1 promotes epithelial-mesenchymal transition in colorectal cancer through ZEB1 activation
SIX1 promotes epithelial-mesenchymal transition in colorectal cancer through ZEB1 activation
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DOI：
10.1038/onc.2011.646
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发表时间：
2012-11-01
期刊：
影响因子：
8
通讯作者：
Inazawa, J.
中科院分区：
文献类型：
--
作者：
Ono, H.;Imoto, I.;Inazawa, J.
上皮-间质转化（EMT）在癌症进展以及正常器官发育和人类病理学（如器官纤维化和伤口愈合）中起重要作用。在这里，我们进行了一个基因表达阵列专门在EMT的结直肠癌（CRC）。从一个全面的基因表达分析，使用上皮和间充质样CRC细胞系，并遵循本体论（GO）分析，SIX 1基因被确定为大肠癌EMT相关基因。使用稳定转染SIX 1表达构建体的SW 480细胞及其对照，我们证明SIX 1过表达抑制CDH 1表达并促进CRC中的EMT。CRC细胞中SIX 1诱导的CDH 1抑制和EMT至少部分与转录后ZEB 1激活和miR-200家族转录抑制相关。在CRC的原发性肿瘤中，与功能发现雅阁，在基底膜破坏和肿瘤浸润前沿观察到癌细胞中SIX 1的异常表达，其中肿瘤细胞在体内经历EMT。综上所述，SIX 1过表达被认为发生在癌发生过程中，并且部分地通过抑制miR-200家族表达和激活CRC中的ZEB 1来促进CDH 1表达的抑制和EMT的促进。Oncogene（2012）31，4923-4934; doi：10.1038/onc.2011.646; 2012年1月30日在线发表
Epithelial-mesenchymal transition (EMT) has a major role in cancer progression, as well as normal organ development and human pathology such as organ fibrosis and wound healing. Here, we performed a gene expression array specialized in EMT of colorectal cancer (CRC). From a comprehensive gene expression analysis using epithelial- and mesenchymal-like CRC cell lines, and following the ontology (GO) analysis, SIX1 gene was identified to be an EMT-related gene in CRC. Using SW480 cells stably transfected with a SIX1 expression construct and their control counterparts, we demonstrated that SIX1 overexpression represses CDH1 expression and promotes EMT in CRC. SIX1-induced CDH1 repression and EMT in CRC cells were correlated at least in part with posttranscriptional ZEB1 activation and miR-200-family transcriptional repression. In primary tumors of CRC, in accord with the functional findings, aberrant expression of SIX1 in cancer cells was observed at the disruption of the basement membrane and at the tumor invasive front, where tumor cells underwent EMT in vivo. Taken together, SIX1 overexpression is suggested to occur in carcinogenesis, and contribute to repression of CDH1 expression and promotion of EMT partly through repression of miR-200-family expression and activation of ZEB1 in CRC. Oncogene (2012) 31, 4923-4934; doi:10.1038/onc.2011.646; published online 30 January 2012