Notch activation promotes bone metastasis via SPARC inhibition in adenoid cystic carcinoma.
Oral Dis
; 2023 Mar 23.
Article
de En
| MEDLINE
| ID: mdl-36951790
ABSTRACT
OBJECTIVES:
We aimed to investigate bone metastasis induced by Notch signalling pathway dysregulation and to demonstrate that SPARC is a potential therapeutic target in adenoid cystic carcinoma (AdCC) with Notch dysregulation. MATERIALS ANDMETHODS:
This retrospective study enrolled 144 AdCC patients. RNA-sequencing and enrichment analyses were performed using 32 AdCC samples. Osteonectin/SPARC and the Notch activation indicator Notch intracellular domain (NICD) were detected using immunohistochemistry. Cell proliferation and migration assays were conducted using stably NICD over-expressing cells. The effect of SPARC on osteoclast differentiation in NICD cells was investigated using western blotting, quantitative reverse transcription PCR, tartrate-resistant acid phosphatase staining and resorption assays.RESULTS:
RNA-sequencing analysis showed that genes down-regulated in Notch-mutant AdCCs, such as SPARC, were enriched in ossification and osteoblast differentiation. Most (75/110, 68.2%) Notch1-wild-type AdCCs showed SPARC over-expression, whereas 30 out of 34 (88.2%) Notch1-mutant tumours showed low SPARC expression. SPARC over-expression was then found negatively to be correlated with NICD expression in 144 AdCCs. NICD over-expression promoted cell growth, migration and osteoclast differentiation, which could be partly reversed by exogenous SPARC.CONCLUSIONS:
Notch activation in AdCC contributes to bone metastasis through SPARC inhibition. The study results suggest that SPARC may represent a prognostic biomarker and potential therapeutic target.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Type d'étude:
Observational_studies
Langue:
En
Journal:
Oral Dis
Sujet du journal:
ODONTOLOGIA
Année:
2023
Type de document:
Article
Pays d'affiliation:
Chine