Figure 7. Clinical relevance of nuclear AURKA expression.

(a,b and c) Primary breast cancer cells were isolated from breast cancer tissues derived from ten patients. Nuclear and cytoplasmic fractions were subjected to immunoblotting (IB) analysis (a). The expression of CD24 and CD44 were analysed using flow cytometry (b). Nuclear and cytoplasmic fractions of AURKA were normalized using histone H3 and β-actin, respectively. The nuclear fraction of c-Myc and hnRNP K were normalized using histone H3. The normalized AURKA, c-Myc, hnRNP K and the CD24^low/CD44^high population derived from the same patient were used to compose a scatterplot and linear regression analysis performed (c). (d) Breast cancer tissues were subjected to IHC staining for indicated antibodies. Representative images were acquired with × 10 and × 40 objectives (upper panel). Scale bar, 50 μm. Pearson's χ²-test was used to analyse the correlation between nuclear AURKA and c-Myc/CD24 (lower panel). (e) IHC staining for AURKA and c-Myc was performed on breast cancer tissues. Kaplan–Meier analysis was performed and log-rank test used to make statistical comparisons. (f) During breast cancer development, AURKA is overexpressed and translocates to the nucleus, where the nuclear AURKA acts as a transactivating factor that binds and activates the MYC promoter through its interaction with hnRNP K. Through these mechanisms, nuclear AURKA enhances BCSC phenotype. Importantly, these processes are dependent on the nuclear localization of AURKA rather than its kinase activity. Traditional targeted therapies focus on the inhibition of kinase activity, which may be insufficient for suppressing the kinase-independent oncogenic actions. These new findings suggest that targeting the spatial deregulation of kinase could be a promising strategy for overcoming kinase inhibitor insensitivity.