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Identification of Integrin β1 as a Novel PAG1-Interacting Protein Involved in the Inherent Radioresistance of Human Laryngeal Carcinoma
Inherent radioresistance plays a crucial role in the failure of radiotherapy. Using the inherent radioresistant (Hep-2max) and radiosensitive (Hep-2min) cell lines established from the parental cell line Hep-2, we previously reported that phosphoprotein associated with glycosphingolipid-enriched mic...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Ivyspring International Publisher
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6277618/ https://www.ncbi.nlm.nih.gov/pubmed/30519312 http://dx.doi.org/10.7150/jca.26885 |
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author | Dong, Xiaoxia Luo, Zhiguo Liu, Tiantian Chai, Jingjing Ke, Qing Shen, Li |
author_facet | Dong, Xiaoxia Luo, Zhiguo Liu, Tiantian Chai, Jingjing Ke, Qing Shen, Li |
author_sort | Dong, Xiaoxia |
collection | PubMed |
description | Inherent radioresistance plays a crucial role in the failure of radiotherapy. Using the inherent radioresistant (Hep-2max) and radiosensitive (Hep-2min) cell lines established from the parental cell line Hep-2, we previously reported that phosphoprotein associated with glycosphingolipid-enriched microdomains 1(PAG1) overexpression in laryngeal carcinoma cells was correlated with inherent radioresistant phenotypes. However, the underlying mechanisms of this effect remain unknown. In the present study, we performed a proteomic screen to investigate the interactome of PAG1 in Hep-2max cells resulting in the identification of several interaction partners. Bioinformatic analysis and immunofluorescence experiments indicated the integrin β1 to be a crucial interaction partner of PAG1. PAG1 was also highly expressed in laryngeal carcinoma radioresistant tissues and showed co-localization with integrin β1. In addition, we demonstrated that integrin β1's binding to PAG1 could be interrupted by MβCD, an inhibitor of lipid rafts formation. Moreover, knockdown of integrin β1 by RNA interference sensitized radioresistant cells to irradiation. Importantly, we identified 2 potential interaction sites (Pro(216)-Arg(232) and Asn(356)-Gly(377)) in the cytoplasmic domain of PAG1 using high throughput peptide arrays. Taken together, these results suggest that the binding of PAG1 to integrin β1 in lipid rafts is essential for inherent radioresistance of human laryngeal carcinoma. |
format | Online Article Text |
id | pubmed-6277618 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-62776182018-12-05 Identification of Integrin β1 as a Novel PAG1-Interacting Protein Involved in the Inherent Radioresistance of Human Laryngeal Carcinoma Dong, Xiaoxia Luo, Zhiguo Liu, Tiantian Chai, Jingjing Ke, Qing Shen, Li J Cancer Research Paper Inherent radioresistance plays a crucial role in the failure of radiotherapy. Using the inherent radioresistant (Hep-2max) and radiosensitive (Hep-2min) cell lines established from the parental cell line Hep-2, we previously reported that phosphoprotein associated with glycosphingolipid-enriched microdomains 1(PAG1) overexpression in laryngeal carcinoma cells was correlated with inherent radioresistant phenotypes. However, the underlying mechanisms of this effect remain unknown. In the present study, we performed a proteomic screen to investigate the interactome of PAG1 in Hep-2max cells resulting in the identification of several interaction partners. Bioinformatic analysis and immunofluorescence experiments indicated the integrin β1 to be a crucial interaction partner of PAG1. PAG1 was also highly expressed in laryngeal carcinoma radioresistant tissues and showed co-localization with integrin β1. In addition, we demonstrated that integrin β1's binding to PAG1 could be interrupted by MβCD, an inhibitor of lipid rafts formation. Moreover, knockdown of integrin β1 by RNA interference sensitized radioresistant cells to irradiation. Importantly, we identified 2 potential interaction sites (Pro(216)-Arg(232) and Asn(356)-Gly(377)) in the cytoplasmic domain of PAG1 using high throughput peptide arrays. Taken together, these results suggest that the binding of PAG1 to integrin β1 in lipid rafts is essential for inherent radioresistance of human laryngeal carcinoma. Ivyspring International Publisher 2018-10-18 /pmc/articles/PMC6277618/ /pubmed/30519312 http://dx.doi.org/10.7150/jca.26885 Text en © Ivyspring International Publisher This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Dong, Xiaoxia Luo, Zhiguo Liu, Tiantian Chai, Jingjing Ke, Qing Shen, Li Identification of Integrin β1 as a Novel PAG1-Interacting Protein Involved in the Inherent Radioresistance of Human Laryngeal Carcinoma |
title | Identification of Integrin β1 as a Novel PAG1-Interacting Protein Involved in the Inherent Radioresistance of Human Laryngeal Carcinoma |
title_full | Identification of Integrin β1 as a Novel PAG1-Interacting Protein Involved in the Inherent Radioresistance of Human Laryngeal Carcinoma |
title_fullStr | Identification of Integrin β1 as a Novel PAG1-Interacting Protein Involved in the Inherent Radioresistance of Human Laryngeal Carcinoma |
title_full_unstemmed | Identification of Integrin β1 as a Novel PAG1-Interacting Protein Involved in the Inherent Radioresistance of Human Laryngeal Carcinoma |
title_short | Identification of Integrin β1 as a Novel PAG1-Interacting Protein Involved in the Inherent Radioresistance of Human Laryngeal Carcinoma |
title_sort | identification of integrin β1 as a novel pag1-interacting protein involved in the inherent radioresistance of human laryngeal carcinoma |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6277618/ https://www.ncbi.nlm.nih.gov/pubmed/30519312 http://dx.doi.org/10.7150/jca.26885 |
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