SPTBN1 Mediates the Cytoplasmic Constraint of PTTG1, Impairing Its Oncogenic Activity in Human Seminoma

SPTBN1 Mediates the Cytoplasmic Constraint of PTTG1, Impairing Its Oncogenic Activity in Human Seminoma

Seminoma is the most common testicular cancer. Pituitary tumor-transforming gene 1 (PTTG1) is a securin showing oncogenic activity in several tumors. We previously demonstrated that nuclear PTTG1 promotes seminoma tumor invasion through its transcriptional activity on matrix metalloproteinase 2 ( )...

Full description

Saved in:
Bibliographic Details
Published in:International journal of molecular sciences Vol. 24; no. 23; p. 16891
Main Authors: Teveroni, Emanuela, Di Nicuolo, Fiorella, Vergani, Edoardo, Oliva, Alessandro, Vodola, Emanuele Pierpaolo, Bianchetti, Giada, Maulucci, Giuseppe, De Spirito, Marco, Cenci, Tonia, Pierconti, Francesco, Gulino, Gaetano, Iavarone, Federica, Urbani, Andrea, Milardi, Domenico, Pontecorvi, Alfredo, Mancini, Francesca
Format: Journal Article
Language:English
Published: Switzerland MDPI AG 01-12-2023
Subjects:
Analysis
Cancer
Genes
Genetic aspects
Hypotheses
interactome
invasiveness
Localization
Medical prognosis
Membrane proteins
Peptides
Proteins
PTTG1
Radiation therapy
seminoma
SPTBN1
Surveillance
TGCTs
Tumors
United Kingdom
Massachusetts
Germany
invasiveness
interactome
seminoma
PTTG1
SPTBN1
TGCTs
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Seminoma is the most common testicular cancer. Pituitary tumor-transforming gene 1 (PTTG1) is a securin showing oncogenic activity in several tumors. We previously demonstrated that nuclear PTTG1 promotes seminoma tumor invasion through its transcriptional activity on matrix metalloproteinase 2 ( ) and E-cadherin ( ). We wondered if specific interactors could affect its subcellular distribution. To this aim, we investigated the PTTG1 interactome in seminoma cell lines showing different PTTG1 nuclear levels correlated with invasive properties. A proteomic approach upon PTTG1 immunoprecipitation uncovered new specific securin interactors. Western blot, confocal microscopy, cytoplasmic/nuclear fractionation, sphere-forming assay, and Atlas database interrogation were performed to validate the proteomic results and to investigate the interplay between PTTG1 and newly uncovered partners. We observed that spectrin beta-chain (SPTBN1) and PTTG1 were cofactors, with SPTBN1 anchoring the securin in the cytoplasm. SPTBN1 downregulation determined PTTG1 nuclear translocation, promoting its invasive capability. Moreover, a PTTG1 deletion mutant lacking SPTBN1 binding was strongly localized in the nucleus. The Atlas database revealed that seminomas that contained higher nuclear PTTG1 levels showed significantly lower SPTBN1 levels in comparison to non-seminomas. In human seminoma specimens, we found a strong PTTG1/SPTBN1 colocalization that decreases in areas with nuclear PTTG1 distribution. Overall, these results suggest that SPTBN1, along with PTTG1, is a potential prognostic factor useful in the clinical management of seminoma.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms242316891