Lung squamous cell carcinoma cells express non-canonically glycosylated IgG that activates integrin-FAK signaling
| Autor: | Weiyan Xu, Jinfeng Chen, Geng Zihan, Xiaoyan Qiu, Qinyuan Liao, Zhengzuo Sheng, Gregory Lee, Jingxuan Zhang, Liang Zhang, Yang Liu, Jingshu Tang, Jing Huang, Youhui Zhang |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Cancer Research Lung Neoplasms medicine.drug_class Integrin Mice SCID Monoclonal antibody Disease-Free Survival Epitope Metastasis Epitopes 03 medical and health sciences Antineoplastic Agents Immunological 0302 clinical medicine In vivo Carcinoma Non-Small-Cell Lung Cell Line Tumor Biomarkers Tumor medicine Animals Humans Lung Integrin alpha6beta4 biology Chemistry Antibodies Monoclonal Cancer Middle Aged Prognosis medicine.disease Xenograft Model Antitumor Assays 030104 developmental biology Oncology Focal Adhesion Kinase 1 Immunoglobulin G 030220 oncology & carcinogenesis biology.protein Cancer research Female Antibody Signal Transduction Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Cancer Letters. 430:148-159 |
| ISSN: | 0304-3835 |
| Popis: | It is increasingly recognized that many human carcinomas express immunoglobulin (Ig) molecules that are distinct from B-cell-derived Ig and play important roles in cancer initiation, progression, and metastasis. However, the molecular mechanisms underlying the functions of cancer-derived Ig remain elusive. Here, we report that lung squamous cell carcinoma (LSCC) cells frequently express high levels of cancer IgG (CIgG) that is specifically recognized by a monoclonal antibody RP215. RP215 recognizes CIgG via a novel epitope that involves an N-glycan modification at a non-consensus site within the CH1 domain. We demonstrate that RP215 recognized CIgG (RP215-CIgG) promotes survival, migration and in vivo growth of LSCC cells, and these oncogenic activities are strongly inhibited by RP215. Mechanistically, RP215-CIgG executes its oncogenic function through interacting with the integrin α6β4 complex and activating the FAK and Src pathways. Notably, the CIgG-integrin-FAK signaling depends on the N-glycan epitope, which is inhibited by RP215. Together, our studies identified a novel CIgG molecule that activates the oncogenic integrin-FAK signaling in LSCC cells. In addition, the activity of CIgG is inhibited by RP215, providing an attractive target for antibody-based therapy of LSCC. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect