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.
journal_name
Int J Mol Scijournal_title
International journal of molecular sciencesauthors
Mendaza S,Fernández-Irigoyen J,Santamaría E,Zudaire T,Guarch R,Guerrero-Setas D,Vidal A,Santos-Salas J,Matias-Guiu X,Ausín K,Díaz de Cerio MJ,Martín-Sánchez Edoi
10.3390/ijms21062125subject
Has Abstractpub_date
2020-03-19 00:00:00issue
6issn
1422-0067pii
ijms21062125journal_volume
21pub_type
杂志文章abstract::Ovarian cancer is the seventh most commonly diagnosed cancer amongst women and has the highest mortality rate of all gynaecological malignancies. It is a heterogeneous disease attributed to one of three cell types found within the reproductive milieu: epithelial, stromal, and germ cell. Each histotype differs in etiol...
journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
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journal_title:International journal of molecular sciences
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journal_title:International journal of molecular sciences
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