An Intrabody against B-Cell Receptor-Associated Protein 31 (BAP31) Suppresses the Glycosylation of the Epithelial Cell-Adhesion Molecule (EpCAM) via Affecting the Formation of the Sec61-Translocon-Associated Protein (TRAP) Complex.
An Intrabody against B-Cell Receptor-Associated Protein 31 (BAP31) Suppresses the Glycosylation of the Epithelial Cell-Adhesion Molecule (EpCAM) via Affecting the Formation of the Sec61-Translocon-Associated Protein (TRAP) Complex.
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DOI：
10.3390/ijms241914787
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发表时间：
2023-09-30
影响因子：
5.6
通讯作者：
Wang B
中科院分区：
文献类型：
--
作者：
Wang T;Wang C;Wang J;Wang B
上皮细胞粘附分子（EpCAM）在癌组织中高度糖基化，EpCAM的致癌功能主要取决于其糖基化程度。预期抑制EpCAM糖基化对癌症具有抑制作用。我们分析了BAP 31与84种肿瘤相关抗原的关系，发现BAP 31与EpCAM蛋白水平呈正相关。构建不再被糖基化修饰的EpCAM N76/111/198 A的三重突变，以确定BAP 31是否对EpCAM的糖基化具有影响。构建含有BAP 31的不同C-末端的质粒以鉴定影响EpCAM糖基化的BAP 31的区域。从人噬菌体单域抗体库中筛选出抗BAP 31（165-205）的抗体，并研究了抗体（VH-F12）对EpCAM糖基化和抗癌的影响。BAP 31通过促进其糖基化来增加EpCAM的蛋白质水平。BAP 31的165 - 205位氨基酸区域在调节EpCAM的糖基化中起重要作用。抗体VH-F12显著抑制EpCAM的糖基化，其随后降低胃癌细胞的粘附，诱导细胞毒性自噬，抑制AKT-PI 3 K-mTOR信号传导途径，并且最终导致体外和体内的增殖抑制。最后，我们阐明了BAP 31通过影响Sec 61易位通道在促进EpCAM的N-糖基化中起关键作用。总之，这些数据表明BAP 31调节EpCAM的N-糖基化，并可能代表癌症治疗的潜在治疗靶点。
The epithelial cell-adhesion molecule (EpCAM) is hyperglycosylated in carcinoma tissue and the oncogenic function of EpCAM primarily depends on the degree of glycosylation. Inhibiting EpCAM glycosylation is expected to have an inhibitory effect on cancer. We analyzed the relationship of BAP31 with 84 kinds of tumor-associated antigens and found that BAP31 is positively correlated with the protein level of EpCAM. Triple mutations of EpCAM N76/111/198A, which are no longer modified by glycosylation, were constructed to determine whether BAP31 has an effect on the glycosylation of EpCAM. Plasmids containing different C-termini of BAP31 were constructed to identify the regions of BAP31 that affects EpCAM glycosylation. Antibodies against BAP31 (165–205) were screened from a human phage single-domain antibody library and the effect of the antibody (VH-F12) on EpCAM glycosylation and anticancer was investigated. BAP31 increases protein levels of EpCAM by promoting its glycosylation. The amino acid region from 165 to 205 in BAP31 plays an important role in regulating the glycosylation of EpCAM. The antibody VH-F12 significantly inhibited glycosylation of EpCAM which, subsequently, reduced the adhesion of gastric cancer cells, inducing cytotoxic autophagy, inhibiting the AKT-PI3K-mTOR signaling pathway, and, finally, resulting in proliferation inhibition both in vitro and in vivo. Finally, we clarified that BAP31 plays a key role in promoting N-glycosylation of EpCAM by affecting the Sec61 translocation channels. Altogether, these data implied that BAP31 regulates the N-glycosylation of EpCAM and may represent a potential therapeutic target for cancer therapy.
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DOI：
10.1007/s13402-015-0247-3
发表时间：
2016-02
期刊：
Cellular oncology (Dordrecht, Netherlands)
影响因子：
--
作者：
Riquelme I;Tapia O;Leal P;Sandoval A;Varga MG;Letelier P;Buchegger K;Bizama C;Espinoza JA;Peek RM;Araya JC;Roa JC
通讯作者：
Roa JC
影响因子：
4.4
作者：
Dormeyer, Wilma;van Hoof, Dennis;Krijgsveld, Jeroen
通讯作者：
Krijgsveld, Jeroen
BAP31 是一种新定义的癌症/睾丸抗原，调节增殖、迁移和侵袭以促进宫颈癌进展。
影响因子：
9
作者：
Dang E;Yang S;Song C;Jiang D;Li Z;Fan W;Sun Y;Tao L;Wang J;Liu T;Zhang C;Jin B;Wang J;Yang K
通讯作者：
Yang K
影响因子：
1.2
作者：
Harkness, Linda;Christiansen, Helle;Kassem, Moustapha
通讯作者：
Kassem, Moustapha
影响因子：
7
作者：
Ong, SE;Blagoev, B;Mann, M
通讯作者：
Mann, M