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WNT8B and WNT9B signaling promote the survival of dormant HGSOC cells through a non-canonical pathway that regulates cancer stem cell phenotypes.

ABSTRACT: Cancer cell dormancy and the resultant resistance to conventional therapies present significant challenges for the successful treatment of high-grade serous ovarian cancer (HGSOC). We used genome wide and specialized sgRNA libraries in CRISPR-based screens to identify critical features of dormancy and metastasis. Our findings demonstrate that Wnt ligands WNT8B and WNT9B are essential for sustaining cell survival during prolonged dormant spheroid culture conditions. Inhibition of Wnt signaling by WNT8B/9B knock out not only compromised spheroid cell viability, but also negatively affected spheroid formation. These Wnt ligands utilize a non-canonical signaling pathway to activate expression of stem cell genes during spheroid dormancy.

ORGANISM(S): Homo sapiens

PROVIDER: GSE306119 | GEO | 2025/08/22

REPOSITORIES: GEO

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