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A role for PP1/NIPP1 in steering migration of human cancer cells

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A role for PP1/NIPP1 in steering migration of human cancer cells. / Martin-Granados, Cristina; Prescott, Alan R.; Van Dessel, Nele ; Van Eynde, Aleyde; Arocena, Miguel; Klaska, Izabela P.; Görnemann, Janice; Beullens, Monique; Bollen, Mathieu; Forrester, John V.; McCaig, Colin D.

In: PLoS ONE, Vol. 7, No. 7, e40769, 2012.

Research output: Contribution to journalArticle

Harvard

Martin-Granados, C, Prescott, AR, Van Dessel, N, Van Eynde, A, Arocena, M, Klaska, IP, Görnemann, J, Beullens, M, Bollen, M, Forrester, JV & McCaig, CD 2012, 'A role for PP1/NIPP1 in steering migration of human cancer cells' PLoS ONE, vol 7, no. 7, e40769., 10.1371/journal.pone.0040769

APA

Martin-Granados, C., Prescott, A. R., Van Dessel, N., Van Eynde, A., Arocena, M., Klaska, I. P., ... McCaig, C. D. (2012). A role for PP1/NIPP1 in steering migration of human cancer cells. PLoS ONE, 7(7), [e40769]. 10.1371/journal.pone.0040769

Vancouver

Martin-Granados C, Prescott AR, Van Dessel N, Van Eynde A, Arocena M, Klaska IP et al. A role for PP1/NIPP1 in steering migration of human cancer cells. PLoS ONE. 2012;7(7). e40769. Available from: 10.1371/journal.pone.0040769

Author

Martin-Granados, Cristina; Prescott, Alan R.; Van Dessel, Nele ; Van Eynde, Aleyde; Arocena, Miguel; Klaska, Izabela P.; Görnemann, Janice; Beullens, Monique; Bollen, Mathieu; Forrester, John V.; McCaig, Colin D. / A role for PP1/NIPP1 in steering migration of human cancer cells.

In: PLoS ONE, Vol. 7, No. 7, e40769, 2012.

Research output: Contribution to journalArticle

Bibtex - Download

@article{eecbee6bbf8440aeacc1f6d6907834b6,
title = "A role for PP1/NIPP1 in steering migration of human cancer cells",
keywords = "Cell Line, Tumor, Cell Movement, Cell Polarity, Centrosome, Electricity, Electrodes, Endoribonucleases, Genes, Neoplasm, Humans, Models, Biological, Phosphoprotein Phosphatases, Protein Binding, Protein Phosphatase 1, RNA-Binding Proteins, Tetracycline, cdc42 GTP-Binding Protein",
author = "Cristina Martin-Granados and Prescott, {Alan R.} and {Van Dessel}, Nele and {Van Eynde}, Aleyde and Miguel Arocena and Klaska, {Izabela P.} and Janice Görnemann and Monique Beullens and Mathieu Bollen and Forrester, {John V.} and McCaig, {Colin D.}",
year = "2012",
doi = "10.1371/journal.pone.0040769",
volume = "7",
number = "7",
journal = "PLoS ONE",
issn = "1932-6203",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - A role for PP1/NIPP1 in steering migration of human cancer cells

A1 - Martin-Granados,Cristina

A1 - Prescott,Alan R.

A1 - Van Dessel,Nele

A1 - Van Eynde,Aleyde

A1 - Arocena,Miguel

A1 - Klaska,Izabela P.

A1 - Görnemann,Janice

A1 - Beullens,Monique

A1 - Bollen,Mathieu

A1 - Forrester,John V.

A1 - McCaig,Colin D.

AU - Martin-Granados,Cristina

AU - Prescott,Alan R.

AU - Van Dessel,Nele

AU - Van Eynde,Aleyde

AU - Arocena,Miguel

AU - Klaska,Izabela P.

AU - Görnemann,Janice

AU - Beullens,Monique

AU - Bollen,Mathieu

AU - Forrester,John V.

AU - McCaig,Colin D.

PY - 2012

Y1 - 2012

N2 - Electrical gradients are present in many developing and regenerating tissues and around tumours. Mimicking endogenous electric fields in vitro has profound effects on the behaviour of many cell types. Intriguingly, specific cell types migrate cathodally, others anodally and some polarise with their long axis perpendicular to the electric vector. These striking phenomena are likely to have in vivo relevance since one of the determining factors during cancer metastasis is the ability to switch between attractive and repulsive migration in response to extracellular guidance stimuli. We present evidence that the cervical cancer cell line HeLa migrates cathodally in a direct current electric field of physiological intensity, while the strongly metastatic prostate cancer cell line PC-3-M migrates anodally. Notably, genetic disruption of protein serine/threonine phosphatase-1 (PP1) and its regulator NIPP1 decrease directional migration in these cell lines. Conversely, the inducible expression of NIPP1 switched the directional response of HeLa cells from cathodal to slightly anodal in a PP1-dependent manner. Remarkably, induction of a hyperactive PP1/NIPP1 holoenzyme, further shifted directional migration towards the anode. We show that PP1 association with NIPP1 upregulates signalling by the GTPase Cdc42 and demonstrate that pharmacological inhibition of Cdc42 in cells overexpressing NIPP1 recovered cathodal migration. Taken together, we provide the first evidence for regulation of directional cell migration by NIPP1. In addition, we identify PP1/NIPP1 as a novel molecular compass that controls directed cell migration via upregulation of Cdc42 signalling and suggest a way by which PP1/NIPP1 may contribute to the migratory properties of cancer cells. © 2012 Martin-Granados et al.

AB - Electrical gradients are present in many developing and regenerating tissues and around tumours. Mimicking endogenous electric fields in vitro has profound effects on the behaviour of many cell types. Intriguingly, specific cell types migrate cathodally, others anodally and some polarise with their long axis perpendicular to the electric vector. These striking phenomena are likely to have in vivo relevance since one of the determining factors during cancer metastasis is the ability to switch between attractive and repulsive migration in response to extracellular guidance stimuli. We present evidence that the cervical cancer cell line HeLa migrates cathodally in a direct current electric field of physiological intensity, while the strongly metastatic prostate cancer cell line PC-3-M migrates anodally. Notably, genetic disruption of protein serine/threonine phosphatase-1 (PP1) and its regulator NIPP1 decrease directional migration in these cell lines. Conversely, the inducible expression of NIPP1 switched the directional response of HeLa cells from cathodal to slightly anodal in a PP1-dependent manner. Remarkably, induction of a hyperactive PP1/NIPP1 holoenzyme, further shifted directional migration towards the anode. We show that PP1 association with NIPP1 upregulates signalling by the GTPase Cdc42 and demonstrate that pharmacological inhibition of Cdc42 in cells overexpressing NIPP1 recovered cathodal migration. Taken together, we provide the first evidence for regulation of directional cell migration by NIPP1. In addition, we identify PP1/NIPP1 as a novel molecular compass that controls directed cell migration via upregulation of Cdc42 signalling and suggest a way by which PP1/NIPP1 may contribute to the migratory properties of cancer cells. © 2012 Martin-Granados et al.

KW - Cell Line, Tumor

KW - Cell Movement

KW - Cell Polarity

KW - Centrosome

KW - Electricity

KW - Electrodes

KW - Endoribonucleases

KW - Genes, Neoplasm

KW - Humans

KW - Models, Biological

KW - Phosphoprotein Phosphatases

KW - Protein Binding

KW - Protein Phosphatase 1

KW - RNA-Binding Proteins

KW - Tetracycline

KW - cdc42 GTP-Binding Protein

UR - http://www.scopus.com/inward/record.url?scp=84864001329&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0040769

DO - 10.1371/journal.pone.0040769

M1 - Article

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 7

VL - 7

ER -

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