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Merck

Tumor microenvironment-induced FOXM1 regulates ovarian cancer stemness.

Cell death & disease (2024-05-29)
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
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.

MATERIALS
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Brand
Product Description

Sigma-Aldrich
Thiostrepton, Thiostrepton, CAS 1393-48-2, is an antibiotic that inhibits protein synthesis by preventing binding of GTP to 50S ribosomal subunit.
Sigma-Aldrich
Monoclonal Anti-Vinculin antibody produced in mouse, clone hVIN-1, ascites fluid
Sigma-Aldrich
Hydrocortisone, BioReagent, suitable for cell culture