Up regulation of the Hippo signalling effector YAP1 is linked to early biochemical recurrence in prostate cancers.

Adaptor Proteins, Signal Transducing / metabolism Aged Apoptosis Cell Proliferation Hippo Signaling Pathway Humans Ki-67 Antigen / metabolism Male Middle Aged Neoplasm Grading Neoplasm Recurrence, Local / metabolism Prostate / metabolism Prostatic Neoplasms / metabolism Protein Serine-Threonine Kinases / metabolism Receptors, Androgen / metabolism Tissue Array Analysis Transcription Factors / metabolism Up-Regulation YAP-Signaling Proteins

Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
02 06 2020
Historique:
received: 12 11 2019
accepted: 05 05 2020
entrez: 4 6 2020
pubmed: 4 6 2020
medline: 15 12 2020
Statut: epublish

Résumé

The transcriptional coactivator YAP1 controls the balance between cell proliferation and apoptosis. YAP1 overexpression is linked to poor prognosis in many cancer types, yet its role in prostate cancer is unknown. Here, we applied YAP1 immunohistochemistry to a tissue microarray containing 17,747 clinical prostate cancer specimens. Cytoplasmic and nuclear YAP1 staining was seen in 81% and 63% of tumours. For both cytoplasmic and nuclear YAP1 staining, high levels were associated with advanced tumour stage, classical and quantitative Gleason grade, positive nodal stage, positive surgical margin, high KI67 labelling index, and early biochemical recurrence (p < 0.0001 each). The prognostic role of YAP1 staining was independent of established prognostic features in multivariate models (p < 0.001). Comparison with previously studied molecular markers identified associations between high YAP1 staining, TMPRSS2:ERG fusion (p < 0.0001), high androgen receptor (AR) expression (p < 0.0001), high Ki67 labelling index (p < 0.0001), and PTEN and 8p deletions (p < 0.0001 each). In conclusion, high YAP1 protein expression is an independent predictor of unfavourable disease course in prostate cancer. That cytoplasmic and nuclear YAP1 staining is equally linked to phenotype and prognosis fits well to a model where YAP1 activation during tumour progression includes up regulation, cytoplasmic accumulation and subsequent translocation to the nucleus.

Identifiants

DOI: 10.1038/s41598-020-65772-w PMID: 32488048 PMC: PMC7265544
pubmed: 32488048
doi: 10.1038/s41598-020-65772-w
pii: 10.1038/s41598-020-65772-w
pmc: PMC7265544
doi:

Substances chimiques

Adaptor Proteins, Signal Transducing 0
Ki-67 Antigen 0
MKI67 protein, human 0
Receptors, Androgen 0
Transcription Factors 0
YAP-Signaling Proteins 0
YAP1 protein, human 0
Protein Serine-Threonine Kinases EC 2.7.11.1

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

8916

Références

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Auteurs

Andreas Marx (A)

Institute of Pathology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
Institute of Pathology, Klinikum Fürth, Fürth, Germany.

Aljoscha Schumann (A)

Institute of Pathology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.

Doris Höflmayer (D)

Institute of Pathology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.

Elena Bady (E)

Institute of Pathology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.

Claudia Hube-Magg (C)

Institute of Pathology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.

Katharina Möller (K)

Institute of Pathology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
ORCID: 0000-0002-9739-4274

Maria Christina Tsourlakis (MC)

Institute of Pathology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.

Stefan Steurer (S)

Institute of Pathology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.

Franziska Büscheck (F)

Institute of Pathology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.

Till Eichenauer (T)

Department of Urology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.

Till S Clauditz (TS)

Institute of Pathology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.

Markus Graefen (M)

Martini-Clinic, Prostate Cancer Centre, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.

Ronald Simon (R)

Institute of Pathology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany. R.Simon@uke.de.
ORCID: 0000-0003-0158-4258

Guido Sauter (G)

Institute of Pathology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.

Jakob R Izbicki (JR)

General, Visceral and Thoracic Surgery Department and Clinic, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.

Hartwig Huland (H)

Martini-Clinic, Prostate Cancer Centre, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.

Hans Heinzer (H)

Martini-Clinic, Prostate Cancer Centre, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.

Alexander Haese (A)

Martini-Clinic, Prostate Cancer Centre, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.

Thorsten Schlomm (T)

Department of Urology, Charité - Universitätsmedizin Berlin, Berlin, Germany.

Christian Bernreuther (C)

Institute of Pathology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.

Patrick Lebok (P)

Institute of Pathology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.

Adam Polonski (A)

Institute of Pathology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
General, Visceral and Thoracic Surgery Department and Clinic, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protéines adaptatrices de la transduction du signal › Up regulation of the Hippo signalling effector...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Up regulation of the Hippo signalling effector...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Mort cellulaire › Mort cellulaire régulée › Apoptose › Up regulation of the Hippo signalling effector...
questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Croissance › Processus de croissance cellulaire › Prolifération cellulaire › Up regulation of the Hippo signalling effector...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Voie de signalisation Hippo › Up regulation of the Hippo signalling effector...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Up regulation of the Hippo signalling effector...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Marqueurs biologiques tumoraux › Antigène KI-67 › Up regulation of the Hippo signalling effector...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › Up regulation of the Hippo signalling effector...
questionsmedicales.fr › Diagnostic › Pronostic › Grading des tumeurs › Up regulation of the Hippo signalling effector...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Processus néoplasiques › Récidive tumorale locale › Up regulation of the Hippo signalling effector...
questionsmedicales.fr › Tissus › Glandes exocrines › Prostate › Up regulation of the Hippo signalling effector...
questionsmedicales.fr › Maladies urogénitales › Tumeurs de l'appareil urogénital › Tumeurs de l'appareil génital mâle › Tumeurs de la prostate › Up regulation of the Hippo signalling effector...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › Up regulation of the Hippo signalling effector...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Récepteurs cytoplasmiques et nucléaires › Récepteurs aux androgènes › Up regulation of the Hippo signalling effector...
questionsmedicales.fr › Techniques d'investigation › Procédures d'analyse sur micropuce › Analyse sur microréseau › Analyse sur puce à tissus › Up regulation of the Hippo signalling effector...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Up regulation of the Hippo signalling effector...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Régulation positive › Up regulation of the Hippo signalling effector...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protéines adaptatrices de la transduction du signal › Protéines de signalisation YAP › Up regulation of the Hippo signalling effector...