Krüppel-like factor 4 mediates cellular migration and invasion by altering RhoA activity.

Q2 Biochemistry, Genetics and Molecular Biology Cell Communication and Adhesion Pub Date : 2018-12-01 DOI:10.1080/15419061.2018.1444034

Philip R Brauer, Jee Hun Kim, Humberto J Ochoa, Elizabeth R Stratton, Kathryn M Black, William Rosencrans, Eliza Stacey, Engda G Hagos

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引用次数: 15

Abstract

Kru¨ppel like factor 4 (KLF4) is a transcription factor that regulates genes related to differentiation and proliferation. KLF4 also plays a role in metastasis via epithelial to mesenchymal transition. Here, we investigate the function of Klf4 in migration and invasion using mouse embryonic fibroblasts and the RKO human colon cancer cell line. Compared to wild-type, cells lacking Klf4 exhibited increased migration-associated phenotypes. In addition, overexpression of Klf4 in Klf4^-/- MEFs attenuated the presence of stress fibers to wild-type levels. An invasion assay suggested that lack of Klf4 resulted in increased invasive capacity. Finally, analysis of RhoA showed elevated RhoA activity in both RKO and MEF cells. Taken together, our results strongly support the novel role of KLF4 in a post-translational regulatory mechanism where KLF4 indirectly modulates the actin cytoskeleton morphology via activity of RhoA in order to inhibit cellular migration and invasion.

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kr ppel样因子4通过改变RhoA活性介导细胞迁移和侵袭。

克隆样因子4 (KLF4)是一种调控细胞分化和增殖相关基因的转录因子。KLF4也在上皮细胞向间质细胞的转移中起作用。本研究利用小鼠胚胎成纤维细胞和RKO人结肠癌细胞系研究Klf4在迁移和侵袭中的功能。与野生型相比，缺乏Klf4的细胞表现出更多的迁移相关表型。此外，Klf4在Klf4-/- mef中的过表达将应力纤维的存在减弱到野生型水平。侵袭试验表明，缺乏Klf4导致侵袭能力增加。最后，RhoA分析显示RKO和MEF细胞中RhoA活性均升高。综上所述，我们的研究结果有力地支持了KLF4在翻译后调节机制中的新作用，其中KLF4通过RhoA的活性间接调节肌动蛋白细胞骨架形态，以抑制细胞迁移和侵袭。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell Communication and Adhesion 生物-生化与分子生物学

CiteScore

2.50

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： Cessation Cell Communication and Adhesion is an international Open Access journal which provides a central forum for research on mechanisms underlying cellular signalling and adhesion. The journal provides a single source of information concerning all forms of cellular communication, cell junctions, adhesion molecules and families of receptors from diverse biological systems. The journal welcomes submission of original research articles, reviews, short communications and conference reports.