Increased Level of Long Non-Coding RNA MALAT1 is a Common Feature of Amoeboid Invasion.

Ladislav Merta,Sven Diederichs,Vladimír Čermák,Aneta Gandalovičová,Jan Brábek,Daniel Rösel,Tony Gutschner,Michal Dibus

doi:10.3390/cancers12051136

Abstract

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.

Highlights

Invasion of cancer cells leading to metastasis is responsible for the vast majority of the 9.6 million cancer-related deaths each year [1,2]
As the increased level of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) expression might be an important feature of amoeboid cells, we further focused on analyzing the possible role of MALAT1 in the induction of the amoeboid phenotype in cancer cells
It is striking that despite the diversity of the datasets, we found an overlap of three genes upregulated in all cells of the amoeboid phenotype—CEMIP and lncRNAs MALAT1 and

Summary

Introduction

Invasion of cancer cells leading to metastasis is responsible for the vast majority of the 9.6 million cancer-related deaths each year [1,2]. Cancer cells can migrate through the extracellular matrix (ECM) collectively or individually. In the case of individually migrating cells, two modes of invasion have been described—mesenchymal and amoeboid. Migrating cancer cells are characterized by an elongated shape, dependence on integrin-mediated adhesion, and secretion of proteolytic enzymes. Amoeboid cells are typically more rounded and frequently display intense membrane blebbing. Due to increased intracellular pressure and high actomyosin contractility, these cells “squeeze” themselves through pores in the ECM without the need to form strong focal

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