PMID- 29778566 OWN - NLM STAT- MEDLINE DCOM- 20190805 LR - 20220409 IS - 1872-7980 (Electronic) IS - 0304-3835 (Linking) VI - 430 DP - 2018 Aug 28 TI - Lung squamous cell carcinoma cells express non-canonically glycosylated IgG that activates integrin-FAK signaling. PG - 148-159 LID - S0304-3835(18)30355-0 [pii] LID - 10.1016/j.canlet.2018.05.024 [doi] AB - 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 C(H)1 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 alpha6beta4 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. CI - Copyright (c) 2018 Elsevier B.V. All rights reserved. FAU - Tang, Jingshu AU - Tang J AD - Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China; Peking University Center for Human Disease Genomics, Beijing, 100191, China. FAU - Zhang, Jingxuan AU - Zhang J AD - Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China; Peking University Center for Human Disease Genomics, Beijing, 100191, China. FAU - Liu, Yang AU - Liu Y AD - Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China; Peking University Center for Human Disease Genomics, Beijing, 100191, China. FAU - Liao, Qinyuan AU - Liao Q AD - Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China; Peking University Center for Human Disease Genomics, Beijing, 100191, China. FAU - Huang, Jing AU - Huang J AD - Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China; Peking University Center for Human Disease Genomics, Beijing, 100191, China. FAU - Geng, Zihan AU - Geng Z AD - Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China; Peking University Center for Human Disease Genomics, Beijing, 100191, China. FAU - Xu, Weiyan AU - Xu W AD - Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China; Peking University Center for Human Disease Genomics, Beijing, 100191, China. FAU - Sheng, Zhengzuo AU - Sheng Z AD - Department of Urology, Second Clinical Medical College of Peking University, Peking University People's Hospital, Beijing, 100044, China. FAU - Lee, Gregory AU - Lee G AD - Andrology Lab, University of British Columbia Centre for Reproductive Health, Vancouver, BC, V5Z 4H4, Canada. FAU - Zhang, Youhui AU - Zhang Y AD - Department of Immunology, Cancer Institute & Hospital, Chinese Academy of Medical Science, Beijing, 100021, China. FAU - Chen, Jinfeng AU - Chen J AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery II, Peking University Cancer Hospital & Institute, Beijing, 100142, China. FAU - Zhang, Liang AU - Zhang L AD - Department of Biomedical Sciences, College of Veterinary Medicine and Life Sciences, City University of Hong Kong, 999077, Hong Kong, China; City University of Hong Kong Shenzhen Research Institute, Shenzhen, Guangdong, 518057, China. Electronic address: liangzhang.28@cityu.edu.hk. FAU - Qiu, Xiaoyan AU - Qiu X AD - Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China; Peking University Center for Human Disease Genomics, Beijing, 100191, China. Electronic address: qiuxy@bjmu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180517 PL - Ireland TA - Cancer Lett JT - Cancer letters JID - 7600053 RN - 0 (Antibodies, Monoclonal) RN - 0 (Antineoplastic Agents, Immunological) RN - 0 (Biomarkers, Tumor) RN - 0 (Epitopes) RN - 0 (Immunoglobulin G) RN - 0 (Integrin alpha6beta4) RN - 0 (glycosylated IgG) RN - EC 2.7.10.2 (Focal Adhesion Kinase 1) RN - EC 2.7.10.2 (PTK2 protein, human) MH - Animals MH - Antibodies, Monoclonal/*pharmacology/therapeutic use MH - Antineoplastic Agents, Immunological/*pharmacology/therapeutic use MH - Biomarkers, Tumor/antagonists & inhibitors/immunology/metabolism MH - Carcinoma, Non-Small-Cell Lung/drug therapy/*pathology MH - Cell Line, Tumor MH - Disease-Free Survival MH - Epitopes/immunology MH - Female MH - Focal Adhesion Kinase 1/metabolism MH - Humans MH - Immunoglobulin G/immunology/*metabolism MH - Integrin alpha6beta4/metabolism MH - Lung/pathology MH - Lung Neoplasms/drug therapy/*pathology MH - Male MH - Mice, SCID MH - Middle Aged MH - Prognosis MH - Signal Transduction/drug effects MH - Xenograft Model Antitumor Assays OTO - NOTNLM OT - Cancer IgG OT - FAK signaling OT - Integrin OT - LSCC EDAT- 2018/05/21 06:00 MHDA- 2019/08/06 06:00 CRDT- 2018/05/21 06:00 PHST- 2018/02/07 00:00 [received] PHST- 2018/05/11 00:00 [revised] PHST- 2018/05/15 00:00 [accepted] PHST- 2018/05/21 06:00 [pubmed] PHST- 2019/08/06 06:00 [medline] PHST- 2018/05/21 06:00 [entrez] AID - S0304-3835(18)30355-0 [pii] AID - 10.1016/j.canlet.2018.05.024 [doi] PST - ppublish SO - Cancer Lett. 2018 Aug 28;430:148-159. doi: 10.1016/j.canlet.2018.05.024. Epub 2018 May 17.