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Article: PAK4 phosphorylates p53 at serine 215 to promote liver cancer metastasis

TitlePAK4 phosphorylates p53 at serine 215 to promote liver cancer metastasis
Authors
Issue Date2016
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
Citation
Cancer Research, 2016, v. 76 n. 19, p. 5732-4572 How to Cite?
AbstractPAK4 kinase contributes to signaling pathways controlling cancer cell transformation, invasion and survival, but its clinicopathological impact has begun to emerge only recently. Here we report that PAK4 overexpression in hepatocellular carcinoma (HCC) conveys aggressive metastatic properties. A novel nuclear splice isoform of PAK4 lacking exon 2 sequences was isolated as part of our studies. By stably overexpressing or silencing PAK4 in HCC cells we showed that it was critical for their migration. Mechanistic investigations in this setting revealed that PAK4 directly phosphorylated p53 at S215, which not only attenuated transcriptional transactivation activity but also inhibited p53-mediated suppression of HCC cell invasion. Taken together, our results showed how PAK4 overexpression in HCC promotes metastatic invasion by regulating p53 phosphorylation.
Persistent Identifierhttp://hdl.handle.net/10722/231428
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372

 

DC FieldValueLanguage
dc.contributor.authorXu, HT-
dc.contributor.authorLai, WL-
dc.contributor.authorLiu, HF-
dc.contributor.authorWong, LLY-
dc.contributor.authorNg, IOL-
dc.contributor.authorChing, YP-
dc.date.accessioned2016-09-20T05:23:02Z-
dc.date.available2016-09-20T05:23:02Z-
dc.date.issued2016-
dc.identifier.citationCancer Research, 2016, v. 76 n. 19, p. 5732-4572-
dc.identifier.issn0008-5472-
dc.identifier.urihttp://hdl.handle.net/10722/231428-
dc.description.abstractPAK4 kinase contributes to signaling pathways controlling cancer cell transformation, invasion and survival, but its clinicopathological impact has begun to emerge only recently. Here we report that PAK4 overexpression in hepatocellular carcinoma (HCC) conveys aggressive metastatic properties. A novel nuclear splice isoform of PAK4 lacking exon 2 sequences was isolated as part of our studies. By stably overexpressing or silencing PAK4 in HCC cells we showed that it was critical for their migration. Mechanistic investigations in this setting revealed that PAK4 directly phosphorylated p53 at S215, which not only attenuated transcriptional transactivation activity but also inhibited p53-mediated suppression of HCC cell invasion. Taken together, our results showed how PAK4 overexpression in HCC promotes metastatic invasion by regulating p53 phosphorylation.-
dc.languageeng-
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/-
dc.relation.ispartofCancer Research-
dc.titlePAK4 phosphorylates p53 at serine 215 to promote liver cancer metastasis-
dc.typeArticle-
dc.identifier.emailLai, WL: bennywll@HKUCC-COM.hku.hk-
dc.identifier.emailNg, IOL: iolng@hku.hk-
dc.identifier.emailChing, YP: ypching@hku.hk-
dc.identifier.authorityNg, IOL=rp00335-
dc.identifier.authorityChing, YP=rp00469-
dc.identifier.doi10.1158/0008-5472.CAN-15-3373-
dc.identifier.hkuros264482-
dc.identifier.volume76-
dc.identifier.issue19-
dc.identifier.spage5732-
dc.identifier.epage4572-
dc.publisher.placeUnited States-

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