Identification of novel regulators of STAT3 activity

Show simple item record Parri, Elina Kuusanmäki, Heikki van Adrichem, Arjan J. Kaustio, Meri Wennerberg, Krister 2020-06-16T07:16:02Z 2020-06-16T07:16:02Z 2020-03-31
dc.identifier.citation Parri , E , Kuusanmäki , H , van Adrichem , A J , Kaustio , M & Wennerberg , K 2020 , ' Identification of novel regulators of STAT3 activity ' , PLoS One , vol. 15 , no. 3 , 0230819 .
dc.identifier.other PURE: 134705077
dc.identifier.other PURE UUID: 75133336-f33e-4188-83a1-6d9f50939fbf
dc.identifier.other RIS: urn:F4810BB02CD7D6EE730D7EA95BC1A57A
dc.identifier.other WOS: 000535937400019
dc.identifier.other ORCID: /0000-0002-9144-5421/work/75945772
dc.description.abstract STAT3 mediates signalling downstream of cytokine and growth factor receptors where it acts as a transcription factor for its target genes, including oncogenes and cell survival regulating genes. STAT3 has been found to be persistently activated in many types of cancers, primarily through its tyrosine phosphorylation (Y705). Here, we show that constitutive STAT3 activation protects cells from cytotoxic drug responses of several drug classes. To find novel and potentially targetable STAT3 regulators we performed a kinase and phosphatase siRNA screen with cells expressing either a hyperactive STAT3 mutant or IL6-induced wild type STAT3. The screen identified cell division cycle 7-related protein kinase (CDC7), casein kinase 2, alpha 1 (CSNK2), discoidin domain-containing receptor 2 (DDR2), cyclin-dependent kinase 8 (CDK8), phosphatidylinositol 4-kinase 2-alpha (PI4KII), C-terminal Src kinase (CSK) and receptor-type tyrosine-protein phosphatase H (PTPRH) as potential STAT3 regulators. Using small molecule inhibitors targeting these proteins, we confirmed dose and time dependent inhibition of STAT3-mediated transcription, suggesting that inhibition of these kinases may provide strategies for dampening STAT3 activity in cancers. en
dc.format.extent 18
dc.language.iso eng
dc.relation.ispartof PLoS One
dc.rights cc_by
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject 1182 Biochemistry, cell and molecular biology
dc.subject ACTIVATION
dc.subject KINASE
dc.subject CANCER
dc.subject INHIBITION
dc.subject MUTATIONS
dc.subject SRC
dc.title Identification of novel regulators of STAT3 activity en
dc.type Article
dc.contributor.organization Institute for Molecular Medicine Finland
dc.contributor.organization University of Helsinki
dc.description.reviewstatus Peer reviewed
dc.relation.issn 1932-6203
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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