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Title: Absence of nuclear p16 is a diagnostic and independent prognostic biomarker in squamous cell carcinoma of the cervix
Author: 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
Ausin, Karina
Díaz de Cerio, María José
Martín-Sánchez, Esperanza
Keywords: Cèl·lules canceroses
Càncer de coll uterí
Cancer cells
Cervix cancer
Issue Date: 19-Mar-2020
Publisher: MDPI
Abstract: 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.
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It is part of: International Journal of Molecular Sciences, 2020, vol. 21, num. 6, p. 2125
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ISSN: 1661-6596
Appears in Collections:Articles publicats en revistes (Patologia i Terapèutica Experimental)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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