Fig. 4: Activation of MUC1-EGFR-IL-6 signaling triggers xenograft tumor relapse and positively correlates with poor outcome of cervical cancer patients with chemotherapy.

a HeLa229 TR/CTL or HeLa229 TR/CRISPR cells were subcutaneously injected to nude mice. When the tumors reached 4 mm × 4 mm, the mice were randomized to groups (n = 6 per group), and injected drugs as indicated intraperitoneally every 3 days for 15 days and the tumor volume was calculated. b IHC score of MUC1, EGFR, and IL-6 expression of pre- and post-NACT cervical cancer tissues are shown (n = 20). c–e Analysis of correlation between the IHC score of MUC1 and EGFR (c), MUC1 and IL-6 (d), EGFR and IL-6 (e) in 20 paired cervical cancer samples with NACT. f Disease-free survival study of MUC1-EGFR-IL-6 (patients with high expression of at least one of the three genes) was analyzed in cervical cancer patients with chemotherapy information from TCGA data sets. (n = 65). g Schematic overview of the MUC1-EGFR-CREB/GRβ axis stimulates IL-6 expression to induce CSCs enrichment and tumor relapse, this effect can be abrogated by erlotinib in paclitaxel-resistant cervical cancer. Differences between linked groups were evaluated by two-tailed Student's t test. *P < 0.05; **P < 0.01; ***P < 0.001; PTX paclitaxel, Erl erlotinib, NACT neoadjuvant chemotherapy.