Absence of nuclear p16 is a diagnostic and independent prognostic biomarker in squamous cell carcinoma of the cervix
The tumor-suppressor protein p16 is paradoxically overexpressed in cervical cancer (CC). Despite its potential as a biomarker, its clinical value and the reasons for its failure in tumor suppression remain unclear. Our purpose was to determine p16 clinical and biological significance in CC. p16 expr...
| Autores: | , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2020 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/172684 |
| Acceso en línea: | https://hdl.handle.net/2445/172684 |
| Access Level: | acceso abierto |
| Palabra clave: | Cèl·lules canceroses Càncer de coll uterí Diagnòstic Cancer cells Cervix cancer Diagnosis |
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Absence of nuclear p16 is a diagnostic and independent prognostic biomarker in squamous cell carcinoma of the cervixMendaza, SaioaFernández Irigoyen, JoaquínSantamaría, EnriqueZudaire, TamaraGuarch Troyas, Rosa MaríaGuerrero-Setas, DavidVidal-Bel, AugustSantos-Salas, JoséMatias-Guiu, Xavier, 1958-Ausin, KarinaDíaz de Cerio, María JoséMartín-Sánchez, EsperanzaCèl·lules cancerosesCàncer de coll uteríDiagnòsticCancer cellsCervix cancerDiagnosisThe tumor-suppressor protein p16 is paradoxically overexpressed in cervical cancer (CC). Despite its potential as a biomarker, its clinical value and the reasons for its failure in tumor suppression remain unclear. Our purpose was to determine p16 clinical and biological significance in CC. p16 expression pattern was examined by immunohistochemistry in 78 CC cases (high-grade squamous intraepithelial lesions (HSILs) and squamous cell carcinomas of the cervix -SCCCs). CC cell proliferation and invasion were monitored by real-time cell analysis and Transwell® invasion assay, respectively. Cytoplasmic p16 interactors were identified from immunoprecipitated extracts by liquid chromatography-tandem mass spectrometry, and colocalization was confirmed by double-immunofluorescence. We observed that SCCCs showed significantly more cytoplasmic than nuclear p16 expression than HSILs. Importantly, nuclear p16 absence significantly predicted poor outcome in SCCC patients irrespective of other clinical parameters. Moreover, we demonstrated that cytoplasmic p16 interacted with CDK4 and other unreported proteins, such as BANF1, AKAP8 and AGTRAP, which could sequester p16 to avoid nuclear translocation, and then, impair its anti-tumor function. Our results suggest that the absence of nuclear p16 could be a diagnostic biomarker between HSIL and SCCC, and an independent prognostic biomarker in SCCC; and explain why p16 overexpression fails to stop CC growth.MDPI2020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/172684Articles publicats en revistes (Patologia i Terapèutica Experimental)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.3390/ijms21062125International Journal of Molecular Sciences, 2020, vol. 21, num. 6, p. 2125https://doi.org/10.3390/ijms21062125cc-by (c) Mendaza, Saioa et al., 2020http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1726842026-05-27T06:46:51Z |
| dc.title.none.fl_str_mv |
Absence of nuclear p16 is a diagnostic and independent prognostic biomarker in squamous cell carcinoma of the cervix |
| title |
Absence of nuclear p16 is a diagnostic and independent prognostic biomarker in squamous cell carcinoma of the cervix |
| spellingShingle |
Absence of nuclear p16 is a diagnostic and independent prognostic biomarker in squamous cell carcinoma of the cervix Mendaza, Saioa Cèl·lules canceroses Càncer de coll uterí Diagnòstic Cancer cells Cervix cancer Diagnosis |
| title_short |
Absence of nuclear p16 is a diagnostic and independent prognostic biomarker in squamous cell carcinoma of the cervix |
| title_full |
Absence of nuclear p16 is a diagnostic and independent prognostic biomarker in squamous cell carcinoma of the cervix |
| title_fullStr |
Absence of nuclear p16 is a diagnostic and independent prognostic biomarker in squamous cell carcinoma of the cervix |
| title_full_unstemmed |
Absence of nuclear p16 is a diagnostic and independent prognostic biomarker in squamous cell carcinoma of the cervix |
| title_sort |
Absence of nuclear p16 is a diagnostic and independent prognostic biomarker in squamous cell carcinoma of the cervix |
| dc.creator.none.fl_str_mv |
Mendaza, Saioa Fernández Irigoyen, Joaquín Santamaría, Enrique Zudaire, Tamara Guarch Troyas, Rosa María Guerrero-Setas, David Vidal-Bel, August Santos-Salas, José Matias-Guiu, Xavier, 1958- Ausin, Karina Díaz de Cerio, María José Martín-Sánchez, Esperanza |
| author |
Mendaza, Saioa |
| author_facet |
Mendaza, Saioa Fernández Irigoyen, Joaquín Santamaría, Enrique Zudaire, Tamara Guarch Troyas, Rosa María Guerrero-Setas, David Vidal-Bel, August Santos-Salas, José Matias-Guiu, Xavier, 1958- Ausin, Karina Díaz de Cerio, María José Martín-Sánchez, Esperanza |
| author_role |
author |
| author2 |
Fernández Irigoyen, Joaquín Santamaría, Enrique Zudaire, Tamara Guarch Troyas, Rosa María Guerrero-Setas, David Vidal-Bel, August Santos-Salas, José Matias-Guiu, Xavier, 1958- Ausin, Karina Díaz de Cerio, María José Martín-Sánchez, Esperanza |
| author2_role |
author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Cèl·lules canceroses Càncer de coll uterí Diagnòstic Cancer cells Cervix cancer Diagnosis |
| topic |
Cèl·lules canceroses Càncer de coll uterí Diagnòstic Cancer cells Cervix cancer Diagnosis |
| description |
The tumor-suppressor protein p16 is paradoxically overexpressed in cervical cancer (CC). Despite its potential as a biomarker, its clinical value and the reasons for its failure in tumor suppression remain unclear. Our purpose was to determine p16 clinical and biological significance in CC. p16 expression pattern was examined by immunohistochemistry in 78 CC cases (high-grade squamous intraepithelial lesions (HSILs) and squamous cell carcinomas of the cervix -SCCCs). CC cell proliferation and invasion were monitored by real-time cell analysis and Transwell® invasion assay, respectively. Cytoplasmic p16 interactors were identified from immunoprecipitated extracts by liquid chromatography-tandem mass spectrometry, and colocalization was confirmed by double-immunofluorescence. We observed that SCCCs showed significantly more cytoplasmic than nuclear p16 expression than HSILs. Importantly, nuclear p16 absence significantly predicted poor outcome in SCCC patients irrespective of other clinical parameters. Moreover, we demonstrated that cytoplasmic p16 interacted with CDK4 and other unreported proteins, such as BANF1, AKAP8 and AGTRAP, which could sequester p16 to avoid nuclear translocation, and then, impair its anti-tumor function. Our results suggest that the absence of nuclear p16 could be a diagnostic biomarker between HSIL and SCCC, and an independent prognostic biomarker in SCCC; and explain why p16 overexpression fails to stop CC growth. |
| publishDate |
2020 |
| dc.date.none.fl_str_mv |
2020 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
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article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/2445/172684 |
| url |
https://hdl.handle.net/2445/172684 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Reproducció del document publicat a: https://doi.org/10.3390/ijms21062125 International Journal of Molecular Sciences, 2020, vol. 21, num. 6, p. 2125 https://doi.org/10.3390/ijms21062125 |
| dc.rights.none.fl_str_mv |
cc-by (c) Mendaza, Saioa et al., 2020 http://creativecommons.org/licenses/by/3.0/es info:eu-repo/semantics/openAccess |
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cc-by (c) Mendaza, Saioa et al., 2020 http://creativecommons.org/licenses/by/3.0/es |
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openAccess |
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application/pdf |
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MDPI |
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MDPI |
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Articles publicats en revistes (Patologia i Terapèutica Experimental) reponame:Dipòsit Digital de la UB instname:Universidad de Barcelona |
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Universidad de Barcelona |
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Dipòsit Digital de la UB |
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