Tn antigen promotes human colorectal cancer metastasis via H-Ras mediated epithelial-mesenchymal transition activation.
作者： Zhe Liu , Jian Liu , Xichen Dong , Xin Hu , Yuliang Jiang
DOI: 10.1111/JCMM.14117
关键词:
摘要: Tn antigen is a truncated O-glycan, frequently detected in colorectal cancer (CRC), but its precise role CRC metastasis not well addressed. Here we investigated the effects of Core 1 β3Gal-T specific molecular chaperone (Cosmc) deletion-mediated exposure on and underlying mechanism. We first used CRISPR/Cas9 technology to knockout Cosmc, which required for normal O-glycosylation, thereby obtained Tn-positive cells. then biological consequences expression CRC. The results showed that cells exhibited an enhanced metastatic capability both in vitro in vivo. A further analysis indicated induced typical activation epithelial-mesenchymal transition (EMT). Mechanistically, found H-Ras, known drive EMT, was markedly up-regulated cells, whereas knockdown H-Ras suppressed EMT. Furthermore, confirmed LS174T (Tn-positive) transfected with wild-type thus expressing no antigen, had down-regulation subsequent inhibition EMT process. In addition, 438 samples TCGA cohort demonstrated Cosmc reversely correlated underscoring significance antigen-H-Ras signalling patients. These data promotes metastasis, possibly mediated by H-Ras-induced activation.
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