The protein phosphatase 4 - PEA15 axis regulates the survival of breast cancer cells

Hdl Handle:
http://hdl.handle.net/10034/613850
Title:
The protein phosphatase 4 - PEA15 axis regulates the survival of breast cancer cells
Authors:
Mohammed, Hiba N.; Pickard, Mark R.; Mourtada-Maarabouni, Mirna
Abstract:
BACKGROUND: The control of breast cell survival is of critical importance for preventing breast cancer initiation and progression. The activity of many proteins which regulate cell survival is controlled by reversible phosphorylation, so that the relevant kinases and phosphatases play crucial roles in determining cell fate. Several protein kinases act as oncoproteins in breast cancer and changes in their activities contribute to the process of transformation. Through counteracting the activity of oncogenic kinases, the protein phosphatases are also likely to be important players in breast cancer development, but this class of molecules is relatively poorly understood. Here we have investigated the role of the serine/threonine protein phosphatase 4 in the control of cell survival of breast cancer cells. METHODS: The breast cancer cell lines, MCF7 and MDA-MB-231, were transfected with expression vectors encoding the catalytic subunit of protein phosphatase 4 (PP4c) or with PP4c siRNAs. Culture viability, apoptosis, cell migration and cell cycle were assessed. The involvement of phosphoprotein enriched in astrocytes 15kDa (PEA15) in PP4c action was investigated by immunoblotting approaches and by siRNA-mediated silencing of PEA15. RESULTS: In this study we showed that PP4c over-expression inhibited cell proliferation, enhanced spontaneous apoptosis and decreased the migratory and colony forming abilities of breast cancer cells. Moreover, PP4c down-regulation produced complementary effects. PP4c is demonstrated to regulate the phosphorylation of PEA15, and PEA15 itself regulates the apoptosis of breast cancer cells. The inhibitory effects of PP4c on breast cancer cell survival and growth were lost in PEA15 knockdown cells, confirming that PP4c action is mediated, at least in part, through the de-phosphorylation of apoptosis regulator PEA15. CONCLUSION: Our work shows that PP4 regulates breast cancer cell survival and identifies a novel PP4c-PEA15 signalling axis in the control of breast cancer cell survival. The dysfunction of this axis may be important in the development and progression of breast cancer.
Affiliation:
Keele University; University of Chester
Citation:
Mohammed, H. N., Pickard, M. R., & Mourtada-Maarabouni, M. (2016). The protein phosphatase 4 - PEA15 axis regulates the survival of breast cancer cells. Cellular Signalling, 28(9), 1389-1400. DOI: 10.1016/j.cellsig.2016.06.011.
Publisher:
Elsevier
Journal:
Cellular Signalling
Publication Date:
15-Jun-2016
URI:
http://hdl.handle.net/10034/613850
DOI:
10.1016/j.cellsig.2016.06.011
Additional Links:
http://www.ncbi.nlm.nih.gov/pubmed/27317964; http://www.sciencedirect.com/science/article/pii/S0898656816301450
Type:
Article
Language:
en
EISSN:
1873-3913
Appears in Collections:
Institute of Medicine

Full metadata record

DC FieldValue Language
dc.contributor.authorMohammed, Hiba N.en
dc.contributor.authorPickard, Mark R.en
dc.contributor.authorMourtada-Maarabouni, Mirnaen
dc.date.accessioned2016-06-21T16:29:48Zen
dc.date.available2016-06-21T16:29:48Zen
dc.date.issued2016-06-15en
dc.identifier.citationMohammed, H. N., Pickard, M. R., & Mourtada-Maarabouni, M. (2016). The protein phosphatase 4 - PEA15 axis regulates the survival of breast cancer cells. Cellular Signalling, 28(9), 1389-1400. DOI: 10.1016/j.cellsig.2016.06.011.en
dc.identifier.doi10.1016/j.cellsig.2016.06.011en
dc.identifier.otherPMID: 27317964en
dc.identifier.urihttp://hdl.handle.net/10034/613850en
dc.description.abstractBACKGROUND: The control of breast cell survival is of critical importance for preventing breast cancer initiation and progression. The activity of many proteins which regulate cell survival is controlled by reversible phosphorylation, so that the relevant kinases and phosphatases play crucial roles in determining cell fate. Several protein kinases act as oncoproteins in breast cancer and changes in their activities contribute to the process of transformation. Through counteracting the activity of oncogenic kinases, the protein phosphatases are also likely to be important players in breast cancer development, but this class of molecules is relatively poorly understood. Here we have investigated the role of the serine/threonine protein phosphatase 4 in the control of cell survival of breast cancer cells. METHODS: The breast cancer cell lines, MCF7 and MDA-MB-231, were transfected with expression vectors encoding the catalytic subunit of protein phosphatase 4 (PP4c) or with PP4c siRNAs. Culture viability, apoptosis, cell migration and cell cycle were assessed. The involvement of phosphoprotein enriched in astrocytes 15kDa (PEA15) in PP4c action was investigated by immunoblotting approaches and by siRNA-mediated silencing of PEA15. RESULTS: In this study we showed that PP4c over-expression inhibited cell proliferation, enhanced spontaneous apoptosis and decreased the migratory and colony forming abilities of breast cancer cells. Moreover, PP4c down-regulation produced complementary effects. PP4c is demonstrated to regulate the phosphorylation of PEA15, and PEA15 itself regulates the apoptosis of breast cancer cells. The inhibitory effects of PP4c on breast cancer cell survival and growth were lost in PEA15 knockdown cells, confirming that PP4c action is mediated, at least in part, through the de-phosphorylation of apoptosis regulator PEA15. CONCLUSION: Our work shows that PP4 regulates breast cancer cell survival and identifies a novel PP4c-PEA15 signalling axis in the control of breast cancer cell survival. The dysfunction of this axis may be important in the development and progression of breast cancer.en
dc.language.isoenen
dc.publisherElsevieren
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pubmed/27317964en
dc.relation.urlhttp://www.sciencedirect.com/science/article/pii/S0898656816301450en
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectBreast canceren
dc.subjectPEA15en
dc.subjectCell survivalen
dc.subjectPP4en
dc.subjectPP4cen
dc.titleThe protein phosphatase 4 - PEA15 axis regulates the survival of breast cancer cellsen
dc.typeArticleen
dc.identifier.eissn1873-3913en
dc.contributor.departmentKeele University; University of Chesteren
dc.identifier.journalCellular Signallingen
dc.date.accepted2016-06-10en
or.grant.openaccessYesen
rioxxterms.funderMinistry of Higher Education and Scientific Research, Republic of Iraqen
rioxxterms.identifier.projectUnknownen
rioxxterms.versionAMen
rioxxterms.licenseref.startdate2017-06-15en
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