Role of ATF5 in the invasive potential of diverse human cancer cell lines
Role of ATF5 in the invasive potential of diverse human cancer cell lines
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DOI：
10.1016/j.bbrc.2016.04.131
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发表时间：
2016-06-03
影响因子：
3.1
通讯作者：
Haga, Hisashi
中科院分区：
文献类型：
--
作者：
Nukuda, Akihiro;Endoh, Hiroki;Haga, Hisashi
转录激活因子5（ATF 5）是ATF/CAMP反应元件结合蛋白家族的成员。我们的研究小组最近发现，ATF 5表达增加了人肺癌细胞的侵袭力。然而，ATF 5对其他癌细胞系的侵袭潜力的影响仍不清楚。因此，在这项研究中，我们研究了ATF 5在不同人类癌细胞系的侵袭活性中的作用。使用Matrigel侵袭测定评估侵袭性。ATF 5敲低导致八种测试的癌细胞系中的七种的侵袭性降低。这些结果表明，ATF 5在几种癌细胞系中促进侵袭力。此外，在三维（3D）培养条件下评估了ATF 5在侵袭性中的作用。在三维胶原凝胶中，HT-1080和MDA-MB-231细胞表现出高侵袭性，具有梭形形态和高侵袭速度。在这两种细胞系中，ATF 5的敲低导致圆形形态和侵袭速度降低。接下来，我们发现ATF 5诱导整合素-α 2和整合素-β 1表达，整合素-α 2或整合素-β 1的缺失导致圆形形态和侵袭速度降低。我们的研究结果表明，ATF 5通过诱导整合素-α 2和整合素-β 1在几种人癌细胞系中的表达来促进侵袭。(C)2016 Elsevier Inc. All rights reserved.
Activating transcription factor 5 (ATF5) is a member of the ATF/CAMP response element-binding protein family. Our research group recently revealed that ATF5 expression increases the invasiveness of human lung carcinoma cells. However, the effects of ATF5 on the invasive potential of other cancer cells lines remain unclear. Therefore, in this study, we investigated the role of ATF5 in the invasive activity of diverse human cancer cell lines. Invasiveness was assessed using Matrigel invasion assays. ATF5 knockdown resulted in decreased invasiveness in seven of eight cancer cell lines tested. These results suggest that ATF5 promotes invasiveness in several cancer cell lines. Furthermore, the roles of ATF5 in the invasiveness were evaluated in three-dimensional (3D) culture conditions. In 3D collagen gel, HT-1080 and MDA-MB-231 cells exhibited high invasiveness, with spindle morphology and high invasion speed. In both cell lines, knockdown of ATF5 resulted in rounded morphology and decreased invasion speed. Next, we showed that ATF5 induced integrin-alpha 2 and integrin-beta 1 expression and that the depletion of integrin-alpha 2 or integrin-beta 1 resulted in round morphology and decreased invasion speed. Our results suggest that ATF5 promotes invasion by inducing the expression of integrin-alpha 2 and integrin-beta 1 in several human cancer cell lines. (C) 2016 Elsevier Inc. All rights reserved.