Merta Ladislav, Gandalovičová Aneta, Čermák Vladimír, Dibus Michal, Gutschner Tony, Diederichs Sven, Rösel Daniel, Brábek Jan
Department of Cell Biology, Charles University, Viničná 7, 12843 Prague, Czech Republic.
Biotechnology and Biomedicine Centre of the Academy of Sciences and Charles University (BIOCEV), Průmyslová 595, 25242 Vestec u Prahy, Czech Republic.
Cancers (Basel). 2020 May 1;12(5):1136. doi: 10.3390/cancers12051136.
The ability of cancer cells to adopt various migration modes (the plasticity of cancer cell invasiveness) is a substantive obstacle in the treatment of metastasis, yet still an incompletely understood process. We performed a comparison of publicly available transcriptomic datasets from various cell types undergoing a switch between the mesenchymal and amoeboid migration modes. Strikingly, lncRNA MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) was one of three genes that were found upregulated in all amoeboid cells analyzed. Accordingly, downregulation of MALAT1 in predominantly amoeboid cell lines A375m2 and A2058 resulted in decrease of active RhoA (Ras homolog family member A) and was accompanied by the amoeboid-mesenchymal transition in A375m2 cells. Moreover, MALAT1 downregulation in amoeboid cells led to increased cell proliferation. Our work is the first to address the role of MALAT1 in MAT/AMT (mesenchymal to amoeboid transition/amoeboid to mesenchymal transition) and suggests that increased MALAT1 expression is a common feature of amoeboid cells.
癌细胞采用多种迁移模式的能力(癌细胞侵袭的可塑性)是转移治疗中的一个重大障碍,但仍是一个尚未完全了解的过程。我们对来自各种细胞类型的公开转录组数据集进行了比较,这些细胞类型在间充质迁移模式和阿米巴样迁移模式之间进行转换。引人注目的是,lncRNA MALAT1(转移相关的肺腺癌转录本1)是在所分析的所有阿米巴样细胞中上调的三个基因之一。因此,在主要为阿米巴样的细胞系A375m2和A2058中下调MALAT1导致活性RhoA(Ras同源家族成员A)减少,并伴随着A375m2细胞中的阿米巴样-间充质转变。此外,阿米巴样细胞中MALAT1的下调导致细胞增殖增加。我们的工作首次探讨了MALAT1在间充质到阿米巴样转变/阿米巴样到间充质转变(MAT/AMT)中的作用,并表明MALAT1表达增加是阿米巴样细胞的一个共同特征。