Tumor microenvironment-induced FOXM1 regulates ovarian cancer stemness.
Cell Death Dis
; 15(5): 370, 2024 May 28.
Article
en En
| MEDLINE
| ID: mdl-38806454
ABSTRACT
In ovarian tumors, the omental microenvironment profoundly influences the behavior of cancer cells and sustains the acquisition of stem-like traits, with major impacts on tumor aggressiveness and relapse. Here, we leverage a patient-derived platform of organotypic cultures to study the crosstalk between the tumor microenvironment and ovarian cancer stem cells. We discovered that the pro-tumorigenic transcription factor FOXM1 is specifically induced by the microenvironment in ovarian cancer stem cells, through activation of FAK/YAP signaling. The microenvironment-induced FOXM1 sustains stemness, and its inactivation reduces cancer stem cells survival in the omental niche and enhances their response to the PARP inhibitor Olaparib. By unveiling the novel role of FOXM1 in ovarian cancer stemness, our findings highlight patient-derived organotypic co-cultures as a powerful tool to capture clinically relevant mechanisms of the microenvironment/cancer stem cells crosstalk, contributing to the identification of tumor vulnerabilities.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Ováricas
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Células Madre Neoplásicas
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Microambiente Tumoral
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Proteína Forkhead Box M1
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Cell Death Dis
Año:
2024
Tipo del documento:
Article
País de afiliación:
Italia