Shen Jie, Lu Juan, Sui Liyuan, Wang Dan, Yin Meizhen, Hoffmann Inka, Legler Anne, Pflugfelder Gert O
Department of Entomology, China Agricultural University, Beijing, China.
Key Laboratory of Carbon Fiber and Functional Polymers, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, China.
Oncotarget. 2014 Dec 15;5(23):11998-2015. doi: 10.18632/oncotarget.2426.
The transcription factors TBX2 and TBX3 are overexpressed in various human cancers. Here, we investigated the effect of overexpressing the orthologous Tbx genes Drosophila optomotor-blind (omb) and human TBX2 in the epithelium of the Drosophila wing imaginal disc and observed two types of cell motility. Omb/TBX2 overexpressing cells could move within the plane of the epithelium. Invasive cells migrated long-distance as single cells retaining or regaining normal cell shape and apico-basal polarity in spite of attenuated apical DE-cadherin concentration. Inappropriate levels of DE-cadherin were sufficient to drive cell migration in the wing disc epithelium. Omb/TBX2 overexpression and reduced DE-cadherin-dependent adhesion caused the formation of actin-rich lateral cell protrusions. Omb/TBX2 overexpressing cells could also delaminate basally, penetrating the basal lamina, however, without degradation of extracellular matrix. Expression of Timp, an inhibitor of matrix metalloproteases, blocked neither intraepithelial motility nor basal extrusion. Our results reveal an MMP-independent mechanism of cell invasion and suggest a conserved role of Tbx2-related proteins in cell invasion and metastasis-related processes.
转录因子TBX2和TBX3在多种人类癌症中过度表达。在此，我们研究了在果蝇翅成虫盘上皮中过表达直系同源Tbx基因果蝇视动盲（omb）和人类TBX2的影响，并观察到两种类型的细胞运动。过表达Omb/TBX2的细胞可在上皮平面内移动。侵袭性细胞作为单个细胞进行长距离迁移，尽管顶端DE-钙黏蛋白浓度降低，但仍保持或恢复正常细胞形状和顶-基极性。DE-钙黏蛋白水平异常足以驱动翅成虫盘上皮中的细胞迁移。Omb/TBX2过表达和DE-钙黏蛋白依赖性黏附减少导致富含肌动蛋白的侧向细胞突起形成。过表达Omb/TBX2的细胞也可从基底脱层，穿透基膜，然而，细胞外基质并未降解。基质金属蛋白酶抑制剂Timp的表达既不阻断上皮内运动也不阻断基底挤压。我们的结果揭示了一种不依赖基质金属蛋白酶的细胞侵袭机制，并表明Tbx2相关蛋白在细胞侵袭和转移相关过程中具有保守作用。
