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

Cancer Letters
Jingshu TangXiaoyan Qiu

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 att...Continue Reading

Citations

Mar 29, 2019·World Journal of Gastrointestinal Oncology·Zi-Han GengXiao-Yan Qiu
Nov 23, 2019·Cellular & Molecular Immunology·Zihan WangXiaoyan Qiu
Dec 16, 2020·International Journal of Molecular Sciences·Sha YinJing Huang
Apr 13, 2021·Frontiers in Immunology·Ming CuiXiaoyan Qiu

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