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Cancer Lett. 2018 Aug 28;430:148-159. doi: 10.1016/j.canlet.2018.05.024. Epub 2018 May 17.

Lung squamous cell carcinoma cells express non-canonically glycosylated IgG that activates integrin-FAK signaling.

Author information

1
Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China; Peking University Center for Human Disease Genomics, Beijing, 100191, China.
2
Department of Urology, Second Clinical Medical College of Peking University, Peking University People's Hospital, Beijing, 100044, China.
3
Andrology Lab, University of British Columbia Centre for Reproductive Health, Vancouver, BC, V5Z 4H4, Canada.
4
Department of Immunology, Cancer Institute & Hospital, Chinese Academy of Medical Science, Beijing, 100021, China.
5
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery II, Peking University Cancer Hospital & Institute, Beijing, 100142, China.
6
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.
7
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.

Abstract

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.

KEYWORDS:

Cancer IgG; FAK signaling; Integrin; LSCC

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