Fig. 7.

NUAK2 is associated with high-grade human bladder cancer. a, c Expression of NUAK2 and the YAP Signature Genes (YAP SG) is enhanced both in high-grade non-muscle-invasive (HG-NMIBC; n = 13, **p = 0.0071) and muscle-invasive (pT2 MIBC; n = 9, **p = 0.0033) bladder cancers³⁹ as compared to LG-NMIBC (n = 27) using an unpaired t test. b Elevated expression of NUAK2 is correlated with disease recurrence in a cohort⁴¹ of MIBC patient samples with n = 57 disease free and n = 56, recurred samples (*p = 0.0172). Box and whisker plots show the median (line in the box), first and third quartiles (lower and upper ends of the box), and the minimum and maximum values (whiskers in the plot). Dots represent a single patient sample. d A heat map depicting expression of NUAK2 and YAP SG in NMIBC LG (open circle), HG (closed circle), and MIBC pT2 (slashed circle) bladder cancer samples³⁹. e Characterization of high-grade-derived and low-grade-derived bladder cancer cell lines. Scale bar, 25 μm. f NUAK2 mRNA expression is elevated in HG-derived (TCCSUP and T24) BC cell lines as compared to LG lines. Data are plotted as the mean ± SD (n = 3). g–i Blocking NUAK2 activity with 10 μM WZ4003 (g) or NUAK2 expression in stable clones (#5 or #7) using inducible NUAK2 shRNAs (h, i) inhibits the growth of HG BC cell lines as measured by SRB (g) or DAPI (h) staining. Data are plotted as the mean ± SD of a representative experiment, n = 3 (for TCC) or mean ± range of two experiments (for T24)