WW domain-containing oxidoreductase (WWOX), an important tumor suppressor, is essential for regulating cell proliferation and apoptosis. Our study demonstrates that low level of WWOX is associated with the triple-negative subtype of breast cancer (TNBC), which has higher stem cell phenotype and chemoresistance. We evaluated the role of WWOX in regulation of breast cancer stem cells (BCSC) phenotype and chemoresistance. Our results showed that knockdown of WWOX increases the stemness of breast cancer cells. Meanwhile, downregulation of WWOX induces the epithelial–mesenchymal transition (EMT) and chemoresistance of breast cancer cell lines. Our findings revealed the role of the WWOX in the regulation of the BCSC population and chemotherapeutic sensitivity and may provide insights for the development of more effective therapies targeting cancer stem cells in breast cancer.
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