Fig.7.

Inhibition of MEK-ERK-USP10-ZEB1 signaling suppresses CRC metastatic colonization.A, Association of ZEB 1 and USP10 mRNA expression in human colon cancers with transcriptomically-determined consensus molecular subtypes (CMS1-4)(34). Data are from 10 cohorts of patients with stage I-IV colon cancers (n=1483; see supplemental Table S2). P values for ZEB1 (3.57 × 10⁻⁸⁴) and USP10 (7.78 ×10⁻¹¹) by CMS were determined using Stouffer’s test. B, Representative images (H&E sections) of metastatic lung nodules generated by tail vein injection of RKO cells into nude mice. Injected RKO cells included those generated to express control shRNA, USP10 shRNA, ZEB1 shRNA, and combined shRNA of USP10 plus ZEB1. C, Quantification of metastatic lung nodules from mice injected with cell lines described in B. D, Representative image (H&E) of metastatic lung nodules induced by injection of RKO cells expressing control shRNA or USP10 shRNA in presence of vehicle, BRAF inhibitor encorafenib, EGFR inhibitor cetuximab, or their combination. E, Quantification of metastatic lung nodules from experiments outlined in D. Metastatic lung colonies were quantified from lung tissue (n=5) (C,E). Data are presented as mean ±SEM using the one-way ANOVA followed by post hoc Tukey’s test. *, p < 0.05,**, p < 0.01.