PROM2 overexpression induces metastatic potential through epithelial-to-mesenchymal transition and ferroptosis resistance in human cancers.
Clin Transl Med
; 14(3): e1632, 2024 03.
Article
in En
| MEDLINE
| ID: mdl-38515278
ABSTRACT
INTRODUCTION:
Despite considerable therapeutic advances in the last 20 years, metastatic cancers remain a major cause of death. We previously identified prominin-2 (PROM2) as a biomarker predictive of distant metastases and decreased survival, thus providing a promising bio-target. In this translational study, we set out to decipher the biological roles of PROM2 during the metastatic process and resistance to cell death, in particular for metastatic melanoma. METHODS ANDRESULTS:
Methods andresults:
We demonstrated that PROM2 overexpression was closely linked to an increased metastatic potential through the increase of epithelial-to-mesenchymal transition (EMT) marker expression and ferroptosis resistance. This was also found in renal cell carcinoma and triple negative breast cancer patient-derived xenograft models. Using an oligonucleotide anti-sense anti-PROM2, we efficaciously decreased PROM2 expression and prevented metastases in melanoma xenografts. We also demonstrated that PROM2 was implicated in an aggravation loop, contributing to increase the metastatic burden both in murine metastatic models and in patients with metastatic melanoma. The metastatic burden is closely linked to PROM2 expression through the expression of EMT markers and ferroptosis cell death resistance in a deterioration loop.CONCLUSION:
Our results open the way for further studies using PROM2 as a bio-target in resort situations in human metastatic melanoma and also in other cancer types.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Ferroptosis
/
Melanoma
Limits:
Animals
/
Humans
Language:
En
Journal:
Clin Transl Med
/
Clin. trans. med. (Online)
/
Clinical and translational medicine (Online)
Year:
2024
Document type:
Article
Affiliation country:
Country of publication: