Clinic implication of MUC1 O-glycosylation and C1GALT1 in esophagus squamous cell carcinoma
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Esophagus squamous cell carcinoma (ESCC) is one of the most aggressive malignant tumors in the world. Our previous data demonstrates that oncoprotein MUC1 is related with metastasis and poor outcome of ESCC. However, alteration of MUC1 in ESCC remains unclear. Using ONCOMINE and COSMIC databases, we analyzed MUC1 gene copy numbers and gene mutations and found that MUC1 had high expression level but few gene mutations in ESCC. Further study of ESCC samples indicated that MUC1 O-glycosylation levels were higher in tumor tissues than that in para-carcinoma tissues in 10 of 14 pairs of ESCC samples. Moreover, we verified a potential link between MUC1 O-glycosylation and C1GALT1, which was further supported by IHC analysis on 38 ESCC and 19 para-carcinoma samples. More importantly, co-expression of MUC1 Oglycosylation and C1GALT1 presented positive correlations with both lymph node metastasis and survival time of ESCC patients. Our work collectively indicates that C1GALT1 is associated with O-glycosylated MUC1 in ESCC, not only suggesting a diagnostic significance of C1GALT1 and MUC1 O-glycosylation in ESCC, but also opening novel insights into targeting C1GALT1 and MUC1 O-glycosylation to suppress ESCC cells metastasis in patients.
KeywordsMUC1 gene mutation glycosylation CIGALT1 ESCC
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This work was supported by the National Natural Science Foundation of China (81472461) to Lei Huang.
- Aoyagi, K., Minashi, K., Igaki, H., Tachimori, Y., Nishimura, T., Hokamura, N., Ashida, A., Daiko, H., Ochiai, A., Muto, M., et al. (2011). Artificially induced epithelial-mesenchymal transition in surgical subjects: its implications in clinical and basic cancer research. PLoS ONE 6, e18196.CrossRefPubMedPubMedCentralGoogle Scholar
- Chen, C.H., Wang, S.W., Chen, C.W., Huang, M.R., Hung, J.S., Huang, H. C., Lin, H.H., Chen, R.J., Shyu, M.K., and Huang, M.C. (2013). MUFigure C20 overexpression predicts poor prognosis and enhances EGF-induced malignant phenotypes via activation of the EGFR-STAT3 pathway in endometrial cancer. Gynecol Oncol 128, 560–567.CrossRefPubMedGoogle Scholar
- Peery, A.F., Crockett, S.D., Barritt, A.S., Dellon, E.S., Eluri, S., Gangarosa, L.M., Jensen, E.T., Lund, J.L., Pasricha, S., Runge, T., et al. (2015). Burden of gastrointestinal, liver, and pancreatic diseases in the United States. Gastroenterology 149, 1731–1741.e3.CrossRefPubMedPubMedCentralGoogle Scholar
- Su, H., Hu, N., Yang, H.H., Wang, C., Takikita, M., Wang, Q.H., Giffen, C., Clifford, R., Hewitt, S.M., Shou, J.Z., et al. (2011). Global gene expression profiling and validation in esophageal squamous cell carcinoma and its association with clinical phenotypes. Clin Cancer Res 17, 2955–2966.CrossRefPubMedPubMedCentralGoogle Scholar
- You, F., Jiang, L., Zhang, B., Lu, Q., Zhou, Q., Liao, X., Wu, H., Du, K., Zhu, Y., Meng, H., et al. (2016). Phase 1 clinical trial demonstrated that MUC1 positive metastatic seminal vesicle cancer can be effectively eradicated by modified anti-MUC1 chimeric antigen receptor transduced T cells. Sci China Life Sci 59, 386–397.CrossRefPubMedGoogle Scholar