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Article: A novel interplay between oncogenic PFTK1 protein kinase and tumor suppressor TAGLN2 in the control of liver cancer cell motility

TitleA novel interplay between oncogenic PFTK1 protein kinase and tumor suppressor TAGLN2 in the control of liver cancer cell motility
Authors
Keywordsactin
cell migration
hepatocellular carcinoma
PFTK1
TAGLN2
Issue Date2011
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/onc
Citation
Oncogene, 2011, v. 30 n. 44, p. 4464-4475 How to Cite?
AbstractThe PFTK1 gene encodes a cdc2-related serine/threonine protein kinase that has been shown to confer cell migratory properties in hepatocellular carcinoma (HCC). However, the prognostic value and biological mechanism by which PFTK1 promotes HCC motility remain largely unknown. Here, we showed from tissue microarray that common upregulations of PFTK1 in primary HCC tumors (n133/180) correlated significantly with early age onset (≤40 years), advance tumor grading and presence of microvascular invasion (≤P0.05). To understand downstream phosphorylated substrate(s) of PFTK1, phospho-proteins in PFTK1 expressing and knockdown Hep3B cells were profiled by two-dimensional- polyacrylamide gel electrophoresis mass spectrometric analysis. Protein identification of differential spots revealed Β-actin (ACTB) and transgelin2 (TAGLN2) as the two most profound phosphorylated changes affected by PFTK1. We verified the presence of TAGLN2 serine phosphorylation and ACTB tyrosine phosphorylation. Moreover, reduced TAGLN2 and ACTB phosphorylations in PFTK1-suppressed Hep3B corresponded to distinct actin depolymerizations and marked inhibition on cell invasion and motility. Given that TAGLN2 is a tumor suppressor whose function has been ascribed in cancer metastasis, we examined if TAGLN2 is an intermediate substrate in the biological path of PFTK1. We showed in PFTK1-suppressed cells that knockdown of TAGLN2 over-rode the inhibitory effect on cell invasion and motility, and a recovery on actin polymerization was evident. Interestingly, we also found that unphosphorylated TAGLN2 in PFTK1-suppressed cells elicited strong actin-binding ability, a mechanism that possibly halts the actin cytoskeleton dynamics. Site-directed mutagenesis of TAGLN2 suggested that PFTK1 regulates the actin-binding affinity of TAGLN2 through the S83 and S163 residues, which if mutated can significantly affect HCC cell motility. Taken together, our data propose a novel, oncogene-tumor suppressor interplay, where oncogenic PFTK1 confers HCC cell motility through inactivating the actin-binding motile suppressing function of TAGLN2 via phosphorylation. © 2011 Macmillan Publishers Limited All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/160576
ISSN
2015 Impact Factor: 7.932
2015 SCImago Journal Rankings: 4.047
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLeung, WKCen_HK
dc.contributor.authorChing, AKKen_HK
dc.contributor.authorChan, AWHen_HK
dc.contributor.authorPoon, TCWen_HK
dc.contributor.authorMian, Hen_HK
dc.contributor.authorWong, ASTen_HK
dc.contributor.authorTo, KFen_HK
dc.contributor.authorWong, Nen_HK
dc.date.accessioned2012-08-16T06:14:44Z-
dc.date.available2012-08-16T06:14:44Z-
dc.date.issued2011en_HK
dc.identifier.citationOncogene, 2011, v. 30 n. 44, p. 4464-4475en_HK
dc.identifier.issn0950-9232en_HK
dc.identifier.urihttp://hdl.handle.net/10722/160576-
dc.description.abstractThe PFTK1 gene encodes a cdc2-related serine/threonine protein kinase that has been shown to confer cell migratory properties in hepatocellular carcinoma (HCC). However, the prognostic value and biological mechanism by which PFTK1 promotes HCC motility remain largely unknown. Here, we showed from tissue microarray that common upregulations of PFTK1 in primary HCC tumors (n133/180) correlated significantly with early age onset (≤40 years), advance tumor grading and presence of microvascular invasion (≤P0.05). To understand downstream phosphorylated substrate(s) of PFTK1, phospho-proteins in PFTK1 expressing and knockdown Hep3B cells were profiled by two-dimensional- polyacrylamide gel electrophoresis mass spectrometric analysis. Protein identification of differential spots revealed Β-actin (ACTB) and transgelin2 (TAGLN2) as the two most profound phosphorylated changes affected by PFTK1. We verified the presence of TAGLN2 serine phosphorylation and ACTB tyrosine phosphorylation. Moreover, reduced TAGLN2 and ACTB phosphorylations in PFTK1-suppressed Hep3B corresponded to distinct actin depolymerizations and marked inhibition on cell invasion and motility. Given that TAGLN2 is a tumor suppressor whose function has been ascribed in cancer metastasis, we examined if TAGLN2 is an intermediate substrate in the biological path of PFTK1. We showed in PFTK1-suppressed cells that knockdown of TAGLN2 over-rode the inhibitory effect on cell invasion and motility, and a recovery on actin polymerization was evident. Interestingly, we also found that unphosphorylated TAGLN2 in PFTK1-suppressed cells elicited strong actin-binding ability, a mechanism that possibly halts the actin cytoskeleton dynamics. Site-directed mutagenesis of TAGLN2 suggested that PFTK1 regulates the actin-binding affinity of TAGLN2 through the S83 and S163 residues, which if mutated can significantly affect HCC cell motility. Taken together, our data propose a novel, oncogene-tumor suppressor interplay, where oncogenic PFTK1 confers HCC cell motility through inactivating the actin-binding motile suppressing function of TAGLN2 via phosphorylation. © 2011 Macmillan Publishers Limited All rights reserved.en_HK
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/oncen_HK
dc.relation.ispartofOncogeneen_HK
dc.subjectactinen_HK
dc.subjectcell migrationen_HK
dc.subjecthepatocellular carcinomaen_HK
dc.subjectPFTK1en_HK
dc.subjectTAGLN2en_HK
dc.subject.meshCarcinoma, Hepatocellular - genetics-
dc.subject.meshCell Movement - genetics-
dc.subject.meshCyclin-Dependent Kinases - metabolism-
dc.subject.meshLiver Neoplasms - genetics-
dc.subject.meshMicrofilament Proteins - metabolism-
dc.titleA novel interplay between oncogenic PFTK1 protein kinase and tumor suppressor TAGLN2 in the control of liver cancer cell motilityen_HK
dc.typeArticleen_HK
dc.identifier.emailWong, AST: awong1@hkucc.hku.hken_HK
dc.identifier.authorityWong, AST=rp00805en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/onc.2011.161en_HK
dc.identifier.pmid21577206-
dc.identifier.scopuseid_2-s2.0-80455174794en_HK
dc.identifier.hkuros203398en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-80455174794&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume30en_HK
dc.identifier.issue44en_HK
dc.identifier.spage4464en_HK
dc.identifier.epage4475en_HK
dc.identifier.isiWOS:000296733200002-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridLeung, WKC=36682598700en_HK
dc.identifier.scopusauthoridChing, AKK=35083263600en_HK
dc.identifier.scopusauthoridChan, AWH=25930306100en_HK
dc.identifier.scopusauthoridPoon, TCW=7006151710en_HK
dc.identifier.scopusauthoridMian, H=54404912300en_HK
dc.identifier.scopusauthoridWong, AST=23987963300en_HK
dc.identifier.scopusauthoridTo, KF=7101911940en_HK
dc.identifier.scopusauthoridWong, N=7202836653en_HK
dc.identifier.citeulike9324682-

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