Inhibition of MUC1-C entering nuclear suppresses MYC expression and attenuates malignant growth in esophageal squamous cell carcinoma

Zhongwei Xin,* Gongsun Xin,* Mo Shi, Liang Song, Qiang Wang, Bin Jiang, Xiangyan Liu Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, People’s Republic of China *These authors contributed equally to this work Background: The mucin 1 (MUC1) heterodimeric protein (N-terminal subunit and C-terminal subunit) is aberrantly overexpressed in esophageal squamous cell carcinoma (ESCC) and has been linked to poor outcomes in this disease. The detailed mechanism(s), however, remains unclear. In this article, we investigate the effects of the MUC1 C-terminal transmembrane subunit (MUC1-C) through the inhibitor GO-201, which inhibits MUC1-C targeting to nuclear. Patients and methods: The expression of MUC1-C and MYC in the ESCC samples and cell lines was detected by immunohistochemistry, immunofluorescence and western blotting. MYC mRNA level was determined by using quantitative real-time polymerase chain reaction. In addition, Cell Counting Kit-8, clonogenic assay, transwell assay and tumor xenograft in nude mice assay were utilized to determine the role of MUC1-C in proliferation, invasion and migration of ESCC cells. Results: The level of MUC1-C in nuclear and MYC in whole cells in the ESCC tissue is significantly higher than that in the noncancerous tissue. Treatment of MUC1-C-overexpressing ESCC cells with GO-201 was associated with downregulation of MYC expression and induction of apoptosis. Besides, in vitro and in vivo assays have both shown that inhibiting MUC1-C targeting to the nucleus by the GO-201 significantly decreased the abilities of proliferation, invasion and migration in ESCC cells. Conclusion: Our findings suggest that MUC1-C targeting to the nucleus plays an important role in suppressing the malignant growth of ESCC and indicate that MUC1-C is a potential target for the treatment of ESCC. Keywords: MUC1 C-terminal subunit (MUC1-C), MYC, esophageal squamous cell carcinoma (ESCC), GO-201, malignant growth