The inhibition of centromere protein K causes anticancer effects in breast carcinoma via effects on the FAK/PI3K/AKT/mTOR pathway.

The overexpression of centromere protein K (CENPK) is a major contributor to the malignant progression of numerous cancers. To date, the detailed functions and mechanisms of CENPK in breast carcinoma are not fully elucidated. The goals of this project were to comprehensively address the relevance of CENPK in breast carcinoma. The initial investigation by TCGA analysis revealed a high expression level of CENPK in breast carcinoma. Subsequently, an immunoblotting assay confirmed that CENPK is highly expressed in the clinical samples of breast carcinoma. In vitro experiments elucidated that the inhibition of CENPK produced substantial anticancer effects, including a reduction of proliferation, the inhibition of epithelial-mesenchymal transition, the induction of cell cycle arrest and chemosensitivity. Mechanism research unveiled a role for CENPK in mediating the focal adhesion kinase (FAK1)/PI3K/AKT/mTOR pathway. Inhibiting the FAK/PI3K/AKT/mTOR pathway was able to reverse CENPK-elicited cancer-promoting effects. Additionally, CENPK-silenced breast carcinoma cells exhibited low tumorigenicity in vivo. In summary, our data demonstrated that CENPK inhibition provided an excellent anticancer effect for breast carcinoma by regulating FAK/PI3K/AKT/mTOR pathway. This work illustrates a novel molecular mechanism for CENPK in breast carcinoma and suggests CENPK inhibition as a promising targeted therapy for breast carcinoma.