Journal
JOURNAL OF CANCER
Volume 9, Issue 15, Pages 2666-2677Publisher
IVYSPRING INT PUBL
DOI: 10.7150/jca.25252
Keywords
C1GalT1; esophageal cancer; radioresistance; beta 1-integrin; glycosylation
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Funding
- National Natural Science Foundation of China [81502666]
- Initial Project for Post-Graduates of Hubei University of Medicine [2016QDJZR10]
- Natural Science Foundation of Hubei Provincial Department of Education [Q20162115, B2017118]
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Radiotherapy has played a limited role for the treatment of human esophageal cancer owing to the risk of tumor radioresistance. Core 1 beta 1, 3-galactosyltransferase (C1GalT1), which catalyzes the formation of core 1 O-glycan structures, is frequently overexpressed during tumorigenesis. However, the exact effects and mechanisms of C1GalT1 in the radioresistance of esophageal cancer remain unclear. In this study, Public databases and our data revealed that C1GalT1 expression was up-regulated in esophageal cancer tissues and was associated with poor survival. Upon irradiation, we found that esophageal cancer cells with high levels of C1GalT1 could tolerate cell death and had increased resistance to radiotherapy. Irradiation also promoted the expression of C1GalT1 and core 1 O-glycan structures. C1GalT1 knockdown increased the radiosensitivity of esophageal cancer cells, and attenuated irradiation-enhanced migration and invasion. Mechanistic investigations showed that C1GalT1 modified O-glycan structures on beta 1-integrin and regulated its downstream focal adhesion kinase (FAK) signaling. Furthermore, beta 1-integrin-blocking antibody and FAK inhibitor enhanced radiation-induced apoptosis in esophageal cancer cells. Together, our results indicate that C1GalT1 is a major determinant of radioresistance via modulation of beta 1-integrin glycosylation. C1GalT1 may be a potent molecular target for enhancing the efficacy of radiotherapy.
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