Fig. 9: Loss of NUMB expression correlates with increased p-cofilin levels in NMIBC patients.
From: Loss of NUMB drives aggressive bladder cancer via a RHOA/ROCK/YAP signaling axis
a Representative IHC staining of phosphorylated cofilin (p-Cofilin) and NUMB in NUMBHigh and NUMBLow high-grade NMIBC TUR specimens. Magnifications (Mag.) of the boxed areas are shown in the lower panels. Bars, 500 µm; Mag, 100 µm. b Quantification of the % of p-cofilin positive cells in 6 NUMBHigh vs. 5 NUMBLow high-grade NMIBC TUR specimens. Values are expressed as mean ± SEM. **, p = 0.0019 by two-sided Welch’s t-test. c Schematic representation of the molecular events influencing the Hippo/YAP pathway activation state in the bladder urothelium in NUMB-proficient or -deficient conditions. In NUMB-proficient conditions (NUMB proficiency), the presence of NUMB keeps in check RHOA/ROCK signaling to the actin machinery, leading to activation of the Hippo pathway, with ensuing YAP phosphorylation, cytoplasmic retention and transcriptional inactivation. In NUMB-deficient conditions (NUMB deficiency), the absence of NUMB leads to activation of RHOA/ROCK signaling to the actin machinery, which in turn suppresses the Hippo pathway, resulting in nuclear translocation of unphosphorylated YAP and ensuing transcription of its target genes via TEAD interaction. Through its transcriptional targets, CYR61 and CTGF, YAP induces EMT, which likely underlies the acquisition of mesenchymal/invasive traits responsible for the biological aggressiveness of NUMB-deficient BCa. Source data are provided as Source Data file.
