期刊
AGING-US
卷 13, 期 19, 页码 23393-23406出版社
IMPACT JOURNALS LLC
关键词
Cosmc; Apo2L/TRAIL; O-glycosylation; C3GnT; Tn antigen; apoptosis
资金
- Shandong Province Natural Science Foundation of China [ZR2018MH028, ZR2014HM020]
- Shandong medicine and Health Science and Technology Development Plan Project [2016WS0010]
- National Natural Science Foundation of China [30972778]
The study revealed that abnormal O-glycosylation caused by Cosmc mutations can lead to Tn antigen expression. Transfection of Cosmc resulted in reduced proliferation and migration of Tn(+) cells, along with increased sensitivity to apoptosis induced by Apo2L/TRAIL. Differences in O-glycan composition among various Tn(+) cells affect cell behavior and modulate sensitivity to apoptotic stimuli.
Cosmc mutations may cause abnormal O-glycosylation and result in Tn antigen expression. In the current study, it was discovered that proliferation and migration of Tn(+) cells (Jurkat T and LS174T-Tn(+) cells) with mutant Cosmc decreased after transfected Cosmc, and their sensitivity to apoptosis induced by Apo2L/TRAIL increased. Core 1-, 2-, and 3-derived O-glycans were absent in Tn(+) cells. After Cosmc transfection, normal extended core 1-derived O-glycans appeared and were accompanied by increased T-synthase activity. Core 2-derived O-glycans appeared in transfected LS174T-Tn(+) cells, and their structural types and levels were lower than those in LS174T-Tn(-) cells. Core 3-derived O-glycans were present only in LS174T-Tn(-) cells. The activity of C3GnT in LS174T-Tn(+) cells was lower than that in LS174T-Tn(-) cells, and it was absent in Jurkat T cells. Cosmc transfection did not alter C3GnT activity or core 3-derived O-glycans in Jurkat T and LS174T-Tn(+) cells. The results demonstrated that the composition and structure of O-glycans were different among various Tn(+) cells, which not only affected cell malignant behavior but also modulated sensitivity to apoptotic stimuli. Thus, Cosmc transfection may effectively decrease the malignant behavior of Tn(+) tumor cells and enhance their sensitivity to apoptosis when induced by Apo2L/TRAIL through modification of O-glycans.
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