HOXB13 and ALX4 induce SLUG expression for the promotion of EMT and cell invasion in ovarian cancer cells.
HOXB13 and ALX4 induce SLUG expression for the promotion of EMT and cell invasion in ovarian cancer cells.
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DOI：
10.18632/oncotarget.3673
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发表时间：
2015-05-30
期刊：
影响因子：
--
通讯作者：
Senga T
中科院分区：
文献类型：
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作者：
Yuan H;Kajiyama H;Ito S;Chen D;Shibata K;Hamaguchi M;Kikkawa F;Senga T
同源异型蛋白是一类具有同源异型盒结构域的转录因子家族，在许多物种的胚胎发育过程中发挥着重要作用。越来越多的研究表明同源异型蛋白在多种肿瘤中异常表达，其功能可能是肿瘤的促进因子，也可能是肿瘤的抑制因子。在这项研究中，我们发现两种同源异型蛋白HOXB 13和ALX 4与上皮间质转化（EMT）和卵巢癌细胞的侵袭有关。HOXB 13和ALX 4在细胞中形成复合物，并且外源性表达任一蛋白促进EMT和侵袭。相反，任何一种蛋白质的耗竭都抑制了EMT的侵袭和诱导逆转。SLUG是一种C2 H2型锌指转录因子，在各种细胞系中促进EMT。HOXB 13或ALX 4的敲低抑制SLUG表达，并且任一蛋白质的外源表达促进SLUG表达。最后，我们发现SLUG表达对于HOXB 13或ALX 4介导的EMT和侵袭是必需的。我们的研究结果表明HOXB 13/SLUG和ALX 4/SLUG轴是促进卵巢癌细胞EMT和侵袭的新途径。
Homeoproteins, a family of transcription factors that have conserved homeobox domains, play critical roles in embryonic development in a wide range of species. Accumulating studies have revealed that homeoproteins are aberrantly expressed in multiple tumors and function as either tumor promoters or suppressors. In this study, we show that two homeoproteins, HOXB13 and ALX4, are associated with epithelial to mesenchymal transition (EMT) and invasion of ovarian cancer cells. HOXB13 and ALX4 formed a complex in cells, and exogenous expression of either protein promoted EMT and invasion. Conversely, depletion of either protein suppressed invasion and induced reversion of EMT. SLUG is a C2H2-type zinc-finger transcription factor that promotes EMT in various cell lines. Knockdown of HOXB13 or ALX4 suppressed SLUG expression, and exogenous expression of either protein promoted SLUG expression. Finally, we showed that SLUG expression was essential for the HOXB13- or ALX4-mediated EMT and invasion. Our results show that HOXB13/SLUG and ALX4/SLUG axes are novel pathways that promote EMT and invasion of ovarian cancer cells.