ERK2 drives tumour cell migration in three-dimensional microenvironments by suppressing expression of Rab17 and liprin-β2

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Title: ERK2 drives tumour cell migration in three-dimensional microenvironments by suppressing expression of Rab17 and liprin-β2
Authors: Thun, A. von
Birtwistle, Marc R.
Kalna, G.
et al.
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Date: 10-Feb-2012
Abstract: Upregulation of the extracellular signal-regulated kinase (ERK) pathway has been shown to contribute to tumour invasion and progression. Because the two predominant ERK isoforms (ERK1 and ERK2, also known as MAPK3 and MAPK1, respectively) are highly homologous and have indistinguishable kinase activities in vitro, both enzymes were believed to be redundant and interchangeable. To challenge this view, we show that ERK2 silencing inhibits invasive migration of MDA-MB-231 cells, and re-expression of ERK2 but not ERK1 restores the normal invasive phenotype. A detailed quantitative analysis of cell movement on 3D matrices indicates that ERK2 knockdown impairs cellular motility by decreasing the migration velocity as well as increasing the time that cells spend not moving. Using gene expression arrays we found that the expression of the genes for Rab17 and liprin-β2 was increased by knockdown of ERK2 and restored to normal levels following re-expression of ERK2, but not ERK1. Both play inhibitory roles in the invasive behaviour of three independent cancer cell lines. Importantly, knockdown of either Rab17 or liprin-β2 restores invasiveness of ERK2-depleted cells, indicating that ERK2 drives invasion of MDA-MB-231 cells by suppressing expression of these genes.
Type of material: Journal Article
Publisher: The Company of Biologists
Journal: Journal of Cell Science
Volume: 125
Issue: 6
Start page: 1465
End page: 1477
Copyright (published version): 2012 The Company of Biologists
Keywords: ERK2cell migrationinvasioncancerRab17Liprin-b2
DOI: 10.1242/jcs.092916
Language: en
Status of Item: Peer reviewed
Appears in Collections:SBI Research Collection

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