1. N-glycosylation of CD82 at Asn157 is required for suppressing migration and invasion by reversing EMT via Wnt/β-catenin pathway in colon cancer.
- Author
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Zhu, Lin, Chen, Yang, Du, Hang, Cong, Ying, Yan, Weixin, Ma, Keli, and Huang, Xiaohua
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COLON cancer , *TETRASPANIN , *CATENINS , *CELL migration , *POST-translational modification , *COLORECTAL cancer , *WNT signal transduction - Abstract
CD82, a tetraspanin superfamily member, has been identified to be glycosylated at three specific residues (Asn129, Asn157, and Asn198). However, CD82 post-translational modification and its effect on colorectal cancer (CRC) metastasis remain unclear. Here, we constructed various deficient mutants of CD82 N-glycosylation in SW620 cells and demonstrated that the Asn157 site is necessary for CD82 glycosylation in CRC cells migration and LN-dependent adhesion in vitro. Furthermore, we found that CD82 N-glycosylation at the Asn157 site leads to lower expression levels of vimentin and claudin-1 but higher expression levels of E-cadherin, which are the EMT markers; also, there are lower expression levels of phospho-GSK3β and less β-catenin transportation to the nucleus. These findings suggest that CD82 N-glycosylation at the Asn157 site inhibits EMT by down-regulating the Wnt/β-catenin pathway. Moreover, we reported that CD82 with N-glycosylation at a single site of the Asn157 reduces lung metastases in vivo. The results indicate that N-glycosylation of CD82 at the Asn157 site regulates CRC metastasis and adhesion. These observations suggest that the N-glycosylation of CD82 might be a potential therapeutic target for CRC. • Asn157 site is necessary for CD82 N-glycosylation in SW620 cells to inhibit migration and maintain LN-dependent adhesion in vitro. • CD82 N-glycosylation at the Asn157 site leads to lower expression levels of vimentin and claudin-1 but higher expression levels of E-cadherin. • CD82 N-glycosylation at the Asn157 site could inactivate Wnt/β-catenin-mediated EMT signaling. • N-glycosylation of CD82 at the Asn157 site in vivo preserves the suppressing tumor metastasis function of CD82. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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