HOXD3-overexpression increases integrin αvβ3 expression and deprives E-cadherin while it enhances cell motility in A549 cells
HOXD3-overexpression increases integrin αvβ3 expression and deprives E-cadherin while it enhances cell motility in A549 cells
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DOI：
10.1007/s10585-006-9047-5
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发表时间：
2006-12-01
影响因子：
4
通讯作者：
Moriuchi, Tetsuya
中科院分区：
文献类型：
--
作者：
Ohta, Hironori;Hamada, Jun-ichi;Moriuchi, Tetsuya
我们以前已经证明，HOXD 3，同源异型盒基因之一，转导到人肺癌A549细胞，增强细胞运动，侵袭和转移。在本研究中，我们研究了整合素β 3在HOXD 3诱导的A549细胞运动中的作用，HOXD 3过表达上调了整合素β 3。我们首先建立了整合素β 3-转染子，并通过三种不同的测定将其运动活性与HOXD 3转染、对照转染和亲本细胞的运动活性进行比较。整合素β 3-转染子以及HOXD 3-转染子与整合素α v亚基形成异源二聚体，并且与对照转染子或亲本细胞相比，通过趋触性或吞噬动力学追踪测定评估显示高度运动活性。体外伤口愈合试验显示，迁移活性分级为HOXD 3-转染子>整合素β 3-转染子>对照转染子或亲本细胞。E-钙粘蛋白在整合素β 3-转染子中表达，但在HOXD 3-转染子中不表达。在伤口愈合试验中加入E-钙粘蛋白的功能阻断抗体促进了整合素β 3转染子的迁移活性，表明E-钙粘蛋白阻止了细胞从伤口边缘解离。这些结果表明，整合素α v β 3的表达增加和HOXD 3过表达导致的E-钙粘蛋白的丢失是运动性和解离增强的原因。
We have previously shown that transduction of HOXD3, one of homeobox genes, into human lung cancer A549 cells enhances cell motility, invasion and metastasis. In the present study, we examined the roles of integrin beta 3 which was up-regulated by HOXD3-overexpression in the HOXD3-induced motility of A549 cells. We first established integrin beta 3-transfectants and compared their motile activity to those of the HOXD3-transfected, control-transfected and parental cells by three different assays. The integrin beta 3-transfectants as well as the HOXD3-transfectants formed heterodimer with integrin alpha v subunit, and showed highly motile activities assessed by haptotaxis or phagokinetic track assay compared to the control transfectants or parental cells. In vitro wound-healing assay revealed that migratory activities were graded as the HOXD3-transfectants > the integrin beta 3-transfectants > the control transfectants or parental cells. E-cadherin was expressed in the integrin beta 3-transfectants but not expressed in the HOXD3-transfectants. An addition of function-blocking antibody to E-cadherin into the wound-healing assay promoted the migratory activity of the integrin beta 3-transfectants, suggesting that E-cadherin prevented the cells from dissociating from the wound edges. These results indicate that increased expression of integrin alpha v beta 3 and loss of E-cadherin by HOXD3-overexpression are responsible for the enhanced motility and dissociation.