A Self-Propagating c-Met–SOX2 Axis Drives Cancer-Derived IgG Signaling That Promotes Lung Cancer Cell Stemness

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

3 Scopus Citations
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Author(s)

  • Xinmei Huang
  • Shenghua Zhang
  • Jingshu Tang
  • Lina Wu
  • Jingxuan Zhang
  • Yang Liu
  • Jing Huang
  • Hui Dai
  • Weiyan Xu
  • Youhui Zhang
  • Jinfeng Chen
  • Mengshu Cao
  • Xiaoyan Qiu

Detail(s)

Original languageEnglish
Pages (from-to)1866-1882
Journal / PublicationCancer Research
Volume83
Issue number11
Online published29 Mar 2023
Publication statusPublished - 1 Jun 2023

Abstract

Elevated IgG expression in cancer cells has been implicated in exacerbated malignancy and poor clinical prognosis. Accumulating evidence indicates that a nonconventional sialylation modification is critical for the function of cancer-derived IgG, indicating the need for a better understanding of the regulatory mechanisms that control the expression and function of sialylated cancer IgG (SIA-cIgG). Here, we conducted genome-wide CRISPR activation screening and identified OCT4 and SOX2 as the key factors that promote SIA-cIgG expression. Functional investigation revealed that SIA-cIgG reciprocally stimulated SOX2 by activating the c-Met/Akt/Erk signaling axis, constituting a self-propagating loop of SIA-cIgG/c-Met/SOX2/SIA-cIgG signaling. This signaling loop was highly active in stem-like cells from many epithelial cancers and was crucial for cancer stemness in vitro and in vivo. Notably, the monoclonal antibody RP215, which specifically recognizes the Asn162 sialylation-related epitope on SIA-cIgG, effectively blocked the SIA-cIgG-driven signaling loop. Furthermore, RP215 significantly inhibited lung cancer cell stemness and tumor growth in a patient-derived xenograft model. In conclusion, these findings revealed a self-propagating c-Met/SOX2/SIA-cIgG signaling loop that promotes cancer stemness, identifying novel therapeutic strategies for cancer treatment. © 2023 American Association for Cancer Research.

Research Area(s)

  • Cancer-derived IgG, sialylated cancer IgG (SIA-cIgG), cancer stem cells (CSCs), c-Met, SOX2

Bibliographic Note

Information for this record is supplemented by the author(s) concerned.

Citation Format(s)

A Self-Propagating c-Met–SOX2 Axis Drives Cancer-Derived IgG Signaling That Promotes Lung Cancer Cell Stemness. / Huang, Xinmei; Zhang, Shenghua; Tang, Jingshu et al.
In: Cancer Research, Vol. 83, No. 11, 01.06.2023, p. 1866-1882.

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review