一种受发育调控的上皮-间质转化诱导因子LBX1，促进乳腺癌进展。
A developmentally regulated inducer of EMT, LBX1, contributes to breast cancer progression.
作者信息
Yu Min, Smolen Gromoslaw A, Zhang Jianmin, Wittner Ben, Schott Benjamin J, Brachtel Elena, Ramaswamy Sridhar, Maheswaran Shyamala, Haber Daniel A
机构信息
Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA.
出版信息
Genes Dev. 2009 Aug 1;23(15):1737-42. doi: 10.1101/gad.1809309.
Abstract
Epithelial-to-mesenchymal transition (EMT) plays an important role during normal embryogenesis, and it has been implicated in cancer invasion and metastasis. Here, we report that Ladybird homeobox 1 (LBX1), a developmentally regulated homeobox gene, directs expression of the known EMT inducers ZEB1, ZEB2, Snail1, and transforming growth factor beta2 (TGFB2). In mammary epithelial cells, overexpression of LBX1 leads to morphological transformation, expression of mesenchymal markers, enhanced cell migration, increased CD44(high)/CD24(low) progenitor cell population, and tumorigenic cooperation with known oncogenes. In human breast cancer, LBX1 is up-regulated in the unfavorable estrogen receptor (ER)/progesterone (PR)/HER2 triple-negative basal-like subtype. Thus, aberrant expression of LBX1 may lead to the activation of a developmentally regulated EMT pathway in human breast cancer.
摘要
上皮-间质转化（EMT）在正常胚胎发育过程中起重要作用，并且与癌症侵袭和转移有关。在此，我们报告瓢虫同源盒1（LBX1），一个受发育调控的同源盒基因，指导已知的EMT诱导因子锌指E盒结合蛋白1（ZEB1）、锌指E盒结合蛋白2（ZEB2）、蜗牛同源物1（Snail1）和转化生长因子β2（TGFB2）的表达。在乳腺上皮细胞中，LBX1的过表达导致形态转变、间充质标志物的表达、细胞迁移增强、CD44高/CD24低祖细胞群体增加以及与已知癌基因的致瘤协同作用。在人类乳腺癌中，LBX1在不良雌激素受体（ER）/孕激素（PR）/人表皮生长因子受体2（HER2）三阴性基底样亚型中上调。因此，LBX1的异常表达可能导致人类乳腺癌中一条受发育调控的EMT途径的激活。
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