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YAP Dysregulation by Phosphorylation or ΔNp63-mediated Gene Repression Promotes Proliferation, Survival and Migration in Head and Neck Cancer Subsets

Over-expression of Yes-associated protein (YAP), and TP53 family members ΔNp63 and p73 with which YAP may serve as a nuclear co-factor, have been independently detected in subsets of head and neck squamous cell carcinomas (HNSCC). Their potential relationship and functional role of YAP in HNSCC are...

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Autores principales: Ehsanian, Reza, Brown, Matthew, Lu, Hai, Yang, Xinping, Pattatheyil, Arun, Yan, Bin, Duggal, Praveen, Chuang, Ryan, Doondeea, Jessica, Feller, Stephan, Sudol, Marius, Chen, Zhong, Van Waes, Carter
Formato: Texto
Lenguaje:English
Publicado: 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2991596/
https://www.ncbi.nlm.nih.gov/pubmed/20729916
http://dx.doi.org/10.1038/onc.2010.339
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author Ehsanian, Reza
Brown, Matthew
Lu, Hai
Yang, Xinping
Pattatheyil, Arun
Yan, Bin
Duggal, Praveen
Chuang, Ryan
Doondeea, Jessica
Feller, Stephan
Sudol, Marius
Chen, Zhong
Van Waes, Carter
author_facet Ehsanian, Reza
Brown, Matthew
Lu, Hai
Yang, Xinping
Pattatheyil, Arun
Yan, Bin
Duggal, Praveen
Chuang, Ryan
Doondeea, Jessica
Feller, Stephan
Sudol, Marius
Chen, Zhong
Van Waes, Carter
author_sort Ehsanian, Reza
collection PubMed
description Over-expression of Yes-associated protein (YAP), and TP53 family members ΔNp63 and p73 with which YAP may serve as a nuclear co-factor, have been independently detected in subsets of head and neck squamous cell carcinomas (HNSCC). Their potential relationship and functional role of YAP in HNSCC are unknown. Here we reveal 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 decreased expression of ΔNp63 and p73. Conversely, YAP expression is decreased but detectable in the nucleus in association with lower AKT and YAP phosphorylation, and increased ΔNp63 and p73 expression, in another subset. Inhibiting AKT decreased Serine-127 phosphorylation and enhanced nuclear translocation of YAP. ΔNp63 repressed YAP expression and bound its promoter. 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/orΔNp63 are potential targets for enhancing YAP-mediated apoptosis and chemosensitivity in HNSCC.
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spelling pubmed-29915962011-05-18 YAP Dysregulation by Phosphorylation or ΔNp63-mediated Gene Repression Promotes Proliferation, Survival and Migration in Head and Neck Cancer Subsets Ehsanian, Reza Brown, Matthew Lu, Hai Yang, Xinping Pattatheyil, Arun Yan, Bin Duggal, Praveen Chuang, Ryan Doondeea, Jessica Feller, Stephan Sudol, Marius Chen, Zhong Van Waes, Carter Oncogene Article Over-expression of Yes-associated protein (YAP), and TP53 family members ΔNp63 and p73 with which YAP may serve as a nuclear co-factor, have been independently detected in subsets of head and neck squamous cell carcinomas (HNSCC). Their potential relationship and functional role of YAP in HNSCC are unknown. Here we reveal 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 decreased expression of ΔNp63 and p73. Conversely, YAP expression is decreased but detectable in the nucleus in association with lower AKT and YAP phosphorylation, and increased ΔNp63 and p73 expression, in another subset. Inhibiting AKT decreased Serine-127 phosphorylation and enhanced nuclear translocation of YAP. ΔNp63 repressed YAP expression and bound its promoter. 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/orΔNp63 are potential targets for enhancing YAP-mediated apoptosis and chemosensitivity in HNSCC. 2010-08-23 2010-11-18 /pmc/articles/PMC2991596/ /pubmed/20729916 http://dx.doi.org/10.1038/onc.2010.339 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Ehsanian, Reza
Brown, Matthew
Lu, Hai
Yang, Xinping
Pattatheyil, Arun
Yan, Bin
Duggal, Praveen
Chuang, Ryan
Doondeea, Jessica
Feller, Stephan
Sudol, Marius
Chen, Zhong
Van Waes, Carter
YAP Dysregulation by Phosphorylation or ΔNp63-mediated Gene Repression Promotes Proliferation, Survival and Migration in Head and Neck Cancer Subsets
title YAP Dysregulation by Phosphorylation or ΔNp63-mediated Gene Repression Promotes Proliferation, Survival and Migration in Head and Neck Cancer Subsets
title_full YAP Dysregulation by Phosphorylation or ΔNp63-mediated Gene Repression Promotes Proliferation, Survival and Migration in Head and Neck Cancer Subsets
title_fullStr YAP Dysregulation by Phosphorylation or ΔNp63-mediated Gene Repression Promotes Proliferation, Survival and Migration in Head and Neck Cancer Subsets
title_full_unstemmed YAP Dysregulation by Phosphorylation or ΔNp63-mediated Gene Repression Promotes Proliferation, Survival and Migration in Head and Neck Cancer Subsets
title_short YAP Dysregulation by Phosphorylation or ΔNp63-mediated Gene Repression Promotes Proliferation, Survival and Migration in Head and Neck Cancer Subsets
title_sort yap dysregulation by phosphorylation or δnp63-mediated gene repression promotes proliferation, survival and migration in head and neck cancer subsets
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2991596/
https://www.ncbi.nlm.nih.gov/pubmed/20729916
http://dx.doi.org/10.1038/onc.2010.339
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