Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) promotes EGF receptor signaling of oral squamous cell carcinoma metastasis via the complex N-glycosylation
| العنوان: | Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) promotes EGF receptor signaling of oral squamous cell carcinoma metastasis via the complex N-glycosylation |
|---|---|
| المؤلفون: | Dar-Bin Shieh, T. M. Cheng, Kuen Haur Lee, C. A. Changou, C. C. Tu, S. Y. Wu, Tzu Hao Chang, W. L. Tsui, Yuh Ling Chen, Ming Heng Wu, Yih Fung Chen, C. C. Chang, Kuei-Yi Chuang, W. F. Chiang, Szu-Hua Pan |
| المصدر: | Oncogene. 37:116-127 |
| بيانات النشر: | Springer Science and Business Media LLC, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Adult, Male, 0301 basic medicine, Cancer Research, Glycosylation, Lung Neoplasms, Mice, SCID, Biology, GPI-Linked Proteins, N-Acetylglucosaminyltransferases, Epitope, Mice, 03 medical and health sciences, chemistry.chemical_compound, Carcinoembryonic antigen, N-linked glycosylation, Antigens, CD, Cell Movement, Epidermal growth factor, Cell Line, Tumor, Biomarkers, Tumor, Genetics, Animals, Humans, Neoplasm Invasiveness, RNA, Small Interfering, Molecular Biology, Neoplasm Staging, Cell adhesion molecule, Xenograft Model Antitumor Assays, Molecular biology, Tumor antigen, ErbB Receptors, 030104 developmental biology, chemistry, Cancer cell, Carcinoma, Squamous Cell, biology.protein, Mouth Neoplasms, Asparagine, Neoplasm Recurrence, Local, Cell Adhesion Molecules, Signal Transduction |
| الوصف: | Aberrant protein glycosylation could be a distinct surface-marker of cancer cells that influences cancer progression and metastasis because glycosylation can regulate membrane protein folding which alters receptor activation and changes epitope exposure for antibody (Ab) recognition. Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6), a glycophosphoinositol-anchored protein, is a heavily glycosylated tumor antigen. However, the clinical significance and biological effect of CEACAM6 glycosylation has not been addressed in cancers. We recently developed an anti-CEACAM6 Ab (TMU) from an immune llama library which can be engineered to a single-domain (sd)Ab or a heavy-chain (HC)Ab. The TMU HCAb specifically recognized glycosylated CEACAM6 compared to the conventional antibodies. Using the TMU HCAb, we found that glycosylated CEACAM6 was a tumor marker associated with recurrence in early-stage OSCC (oral squamous cell carcinoma) patients. CEACAM6 promoted OSCC cell invasion, migration, cytoskeletal rearrangement, and metastasis via interaction with epidermal growth factor (EGF) receptor (EGFR) and enhancing EGFR activation, clustering and intracellular signaling cascades. These functions were modulated by N-acetylglucosaminyltransferase 5 (MGAT5) which mediated N-glycosylation at Asn256 (N256) of CEACAM6. Finally, the TMU sdAb and HCAb treatment inhibited the migration, invasion and EGF-induced signaling in CEACAM6-overexpressing cells. In conclusion, the complex N-glycosylation of CEACAM6 is critical for EGFR signaling of OSCC invasion and metastasis. Targeting glycosylated CEACAM6 with the TMU sdAb or TMU HCAb could be a feasible therapy for OSCC. |
| تدمد: | 1476-5594 0950-9232 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cc8116f8c21264f03c528943d052bd07Test https://doi.org/10.1038/onc.2017.303Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....cc8116f8c21264f03c528943d052bd07 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14765594 09509232 |
|---|