Fig. 1.

DYRK2 and proteasome are up-regulated in TNBC and promote tumor progression. (A) DYRK2 IHC of TNBC and adjacent normal breast tissue sections from patients. (Scale bar, 100 μm.) (B) DYRK2, (C) RPT3, and (D) PSMB5 differential gene expression in human TNBC and matched normal tissue as available from TCGA (TNBC vs. normal tissue, P value derived from a semipaired modification to the Student’s t test) (see also SI Appendix, Fig. S1). (E) Proteasome was affinity-purified from 1 mg of cell lysate of parental or DYRK2 KO MDA-MB-468 Rpn11-TBHA cells. Proteasome activity was measured with Suc-LLVY-AMC. **P < 0.01 (parental vs. DYRK2 KO, unpaired Student's t test, mean ± SD from n = 3 independent experiments). Immunoblotting of the cell lysates were carried out with indicated antibodies. (F) Experimental flow for TNBC xenograft study in G–I. (G and H) MDA-MB-231 parental or DYRK2 KO or DYRK2 KO + WT rescue cells were injected into the mammary fat pad of J:NU nude mice. Tumor volume was measured twice a week (n = 6 mice per condition), and growth curves were plotted. ***P < 0.001 (compared to parental group, 2-way ANOVA, mean ± SD with Tukey’s multiple comparison). (I) Histological examination of consecutive sections of the tumors (from G and H) with Ki67 and hematoxylin/eosin staining. (Scale bar, 100 μm.)