In summary, we have shown that the association of c-Kit with PHB upregulated phospho-PHBY259 in the lipid raft domain, resulting in subsequent activation of the Notch3—PBX1 and β-catenin—ABCG2 signaling pathways to increase stemness, tumorigenicity and drug resistance in ovarian cancer. Here, PBX1 is linked to ovarian carcinoma.