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Article: YAP dysregulation by phosphorylation or DeltaNp63-mediated gene repression promotes proliferation, survival and migration in head and neck cancer

TitleYAP dysregulation by phosphorylation or DeltaNp63-mediated gene repression promotes proliferation, survival and migration in head and neck cancer
Authors
KeywordsδNp63
apoptosis
cancer
p53
p73
YAP
Issue Date2010
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/onc
Citation
Oncogene, 2010, v. 29 n. 46, p. 6160-6171 How to Cite?
AbstractOverexpression of the Yes-associated protein (YAP), and TP53 family members ΔNp63 and p73, have been independently detected in subsets of head and neck squamous cell carcinomas (HNSCCs). YAP may serve as a nuclear cofactor with ΔNp63 and p73, but the functional role of YAP and their potential relationship in HNSCCs are unknown. In this study, we show that in a subset of HNSCC lines and tumors, YAP expression is increased but localized in the cytoplasm in association with increased AKT and YAP phosphorylation, and with decreased expression of ΔNp63 and p73. In another subset, YAP expression is decreased but detectable in the nucleus in association with lower AKT and YAP phosphorylation, and with increased ΔNp63 and p73 expression. Inhibiting AKT decreased serine-127 phosphorylation and enhanced nuclear translocation of YAP. ΔNp63 bound to the YAP promoter and suppressed its expression. Transfection of a YAP-serine-127-alanine phosphoacceptor-site mutant or ΔNp63 knockdown significantly increased nuclear YAP and cell death. Conversely, YAP knockdown enhanced cell proliferation, survival, migration and cisplatin chemoresistance. Thus, YAP function as a tumor suppressor may alternatively be dysregulated by AKT phosphorylation at serine-127 and cytoplasmic sequestration, or by transcriptional repression by ΔNp63, in different subsets of HNSCC. AKT and/or ΔNp63 are potential targets for enhancing YAP-mediated apoptosis and chemosensitivity in HNSCCs.
Persistent Identifierhttp://hdl.handle.net/10722/210607
ISSN
2023 Impact Factor: 6.9
2023 SCImago Journal Rankings: 2.334
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorEhsanian, R-
dc.contributor.authorBrown, M-
dc.contributor.authorLu, H-
dc.contributor.authorYang, XP-
dc.contributor.authorPattatheyil, A-
dc.contributor.authorYan, B-
dc.contributor.authorDuggal, P-
dc.contributor.authorChuang, R-
dc.contributor.authorDoondeea, J-
dc.contributor.authorFeller, S-
dc.contributor.authorSudol, M-
dc.contributor.authorChen, Z-
dc.contributor.authorVan Waes, C-
dc.date.accessioned2015-06-19T06:42:49Z-
dc.date.available2015-06-19T06:42:49Z-
dc.date.issued2010-
dc.identifier.citationOncogene, 2010, v. 29 n. 46, p. 6160-6171-
dc.identifier.issn0950-9232-
dc.identifier.urihttp://hdl.handle.net/10722/210607-
dc.description.abstractOverexpression of the Yes-associated protein (YAP), and TP53 family members ΔNp63 and p73, have been independently detected in subsets of head and neck squamous cell carcinomas (HNSCCs). YAP may serve as a nuclear cofactor with ΔNp63 and p73, but the functional role of YAP and their potential relationship in HNSCCs are unknown. In this study, we show that in a subset of HNSCC lines and tumors, YAP expression is increased but localized in the cytoplasm in association with increased AKT and YAP phosphorylation, and with decreased expression of ΔNp63 and p73. In another subset, YAP expression is decreased but detectable in the nucleus in association with lower AKT and YAP phosphorylation, and with increased ΔNp63 and p73 expression. Inhibiting AKT decreased serine-127 phosphorylation and enhanced nuclear translocation of YAP. ΔNp63 bound to the YAP promoter and suppressed its expression. Transfection of a YAP-serine-127-alanine phosphoacceptor-site mutant or ΔNp63 knockdown significantly increased nuclear YAP and cell death. Conversely, YAP knockdown enhanced cell proliferation, survival, migration and cisplatin chemoresistance. Thus, YAP function as a tumor suppressor may alternatively be dysregulated by AKT phosphorylation at serine-127 and cytoplasmic sequestration, or by transcriptional repression by ΔNp63, in different subsets of HNSCC. AKT and/or ΔNp63 are potential targets for enhancing YAP-mediated apoptosis and chemosensitivity in HNSCCs.-
dc.languageeng-
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/onc-
dc.relation.ispartofOncogene-
dc.subjectδNp63-
dc.subjectapoptosis-
dc.subjectcancer-
dc.subjectp53-
dc.subjectp73-
dc.subjectYAP-
dc.titleYAP dysregulation by phosphorylation or DeltaNp63-mediated gene repression promotes proliferation, survival and migration in head and neck cancer-
dc.typeArticle-
dc.identifier.emailYan, B: yanbinai6017@gmail.com-
dc.identifier.authorityYan, B=rp01940-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1038/onc.2010.339-
dc.identifier.pmid20729916-
dc.identifier.pmcidPMC2991596-
dc.identifier.scopuseid_2-s2.0-78650202033-
dc.identifier.volume29-
dc.identifier.issue46-
dc.identifier.spage6160-
dc.identifier.epage6171-
dc.identifier.isiWOS:000284356500008-
dc.publisher.placeUnited Kingdom-
dc.identifier.issnl0950-9232-

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