MUC1 promotes lymph node metastasis in esophageal squamous cell carcinoma by downregulating DNAJB6 expression

Background: Aberrant expression of MUC1 correlates with the progression of esophageal squamous cell carcinoma (ESCC), this study aimed to explore the effect of targeting MUC1 by Go-203 on malignant behavior of ESCC and the underlying mechanism.

Methods and results: IHC was used to examine the expression of MUC1 and DNAJB6 in ESCC samples. qRT-PCR and western blotting were used to examine the expression of MUC1 and DNAJB6 in ESCC cell lines. CCK8, wound healing, and transwell assays were used to determine the effect of regulating MUC1/DNAJB6 on the proliferation, migration, and invasion of ESCC cells. The effect of overexpressing/targeting MUC1 on the activation of the Akt/HSF-1 pathway was determined by western blotting. A negative correlation was confirmed between the expression of DNAJB6 and MUC1 in ESCC tissue samples by IHC, and high expression of MUC1 and low expression of DNAJB6 correlated with lymph node metastasis in ESCC patients. Overexpressing MUC1 downregulated the expression of DNAJB6, promoted ESCC proliferation, invasion, migration and activated the Akt pathway, while targeting MUC1 suppressed proliferation, invasion, migration, and the Akt pathway and up-regulated DNAJB6 expression in vitro. Moreover, MUC1 increased the phosphorylation of HSF-1 via the Akt pathway, and inhibiting AKT-HSF-1 increased the expression of DNAJB6 in vitro.

Conclusions: This study indicated that MUC1 could promote tumorigenesis and metastasis in ESCC by downregulating DNAJB6 expression through AKT-HSF-1 pathway.

DNAJB6; MUC1; esophageal squamous cell carcinoma; heat shock factor-1.