Tumor microenvironment-induced FOXM1 regulates ovarian cancer stemness
| Title: | Tumor microenvironment-induced FOXM1 regulates ovarian cancer stemness |
|---|---|
| Authors: | Chiara Battistini, Hilary A. Kenny, Melissa Zambuto, Valentina Nieddu, Valentina Melocchi, Alessandra Decio, Pietro Lo Riso, Carlo Emanuele Villa, Alessia Gatto, Mariacristina Ghioni, Francesca M. Porta, Giuseppe Testa, Raffaella Giavazzi, Nicoletta Colombo, Fabrizio Bianchi, Ernst Lengyel, Ugo Cavallaro |
| Source: | Cell Death and Disease, Vol 15, Iss 5, Pp 1-13 (2024) |
| Publisher Information: | Nature Publishing Group, 2024. |
| Publication Year: | 2024 |
| Collection: | LCC:Cytology |
| Subject Terms: | Cytology, QH573-671 |
| More Details: | 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. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2041-4889 21455619 |
| Relation: | https://doaj.org/toc/2041-4889 |
| DOI: | 10.1038/s41419-024-06767-7 |
| Access URL: | https://doaj.org/article/bbabde530b394fa6aa21455619c9f3bc |
| Accession Number: | edsdoj.bbabde530b394fa6aa21455619c9f3bc |
| Database: | Directory of Open Access Journals |
| ISSN: | 20414889 21455619 |
|---|---|
| DOI: | 10.1038/s41419-024-06767-7 |
| Published in: | Cell Death and Disease |
| Language: | English |