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

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal

4 Scopus Citations
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Author(s)

  • Jingshu Tang
  • Jingxuan Zhang
  • Yang Liu
  • Qinyuan Liao
  • Jing Huang
  • Zihan Geng
  • Weiyan Xu
  • Zhengzuo Sheng
  • Gregory Lee
  • Youhui Zhang
  • Jinfeng Chen
  • Xiaoyan Qiu

Detail(s)

Original languageEnglish
Pages (from-to)148-159
Journal / PublicationCancer Letters
Volume430
Online published17 May 2018
Publication statusPublished - 28 Aug 2018

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.

Research Area(s)

  • Cancer IgG, FAK signaling, Integrin, LSCC

Citation Format(s)

Lung squamous cell carcinoma cells express non-canonically glycosylated IgG that activates integrin-FAK signaling. / Tang, Jingshu; Zhang, Jingxuan; Liu, Yang; Liao, Qinyuan; Huang, Jing; Geng, Zihan; Xu, Weiyan; Sheng, Zhengzuo; Lee, Gregory; Zhang, Youhui; Chen, Jinfeng; Zhang, Liang; Qiu, Xiaoyan.

In: Cancer Letters, Vol. 430, 28.08.2018, p. 148-159.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal