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Tumor microenvironment-induced FOXM1 regulates ovarian cancer stemness
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Journal Article
Tumor microenvironment-induced FOXM1 regulates ovarian cancer stemness
2024
Overview
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.
Publisher
Nature Publishing Group UK,Springer Nature B.V,Nature Publishing Group
Subject
/ 13/100
/ 14/19
/ 38/1
/ 45
/ 45/91
/ Animals
/ Biomedical and Life Sciences
/ Female
/ Focal Adhesion Kinase 1 - genetics
/ Focal Adhesion Kinase 1 - metabolism
/ Forkhead Box Protein M1 - genetics
/ Forkhead Box Protein M1 - metabolism
/ Gene Expression Regulation, Neoplastic - drug effects
/ Humans
/ Mice
/ Neoplastic Stem Cells - drug effects
/ Neoplastic Stem Cells - metabolism
/ Neoplastic Stem Cells - pathology
/ Oncology
/ Ovarian Neoplasms - drug therapy
/ Ovarian Neoplasms - genetics
/ Ovarian Neoplasms - metabolism
/ Ovarian Neoplasms - pathology
/ Signal Transduction - drug effects
/ Tumor Microenvironment - drug effects
/ Tumors
