Cell Death and Disease (Aug 2024)

Neoplastic ICAM-1 protects lung carcinoma from apoptosis through ligation of fibrinogen

  • ShiHui Wang,
  • JunLei Wang,
  • Cui Liu,
  • Lei Yang,
  • XuanQian Tan,
  • ShiYang Chen,
  • Yun Xue,
  • HongBin Ji,
  • GaoXiang Ge,
  • JianFeng Chen

DOI
https://doi.org/10.1038/s41419-024-06989-9
Journal volume & issue
Vol. 15, no. 8
pp. 1 – 15

Abstract

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Abstract Intercellular cell adhesion molecule-1 (ICAM-1) is frequently overexpressed in non-small cell lung cancer (NSCLC) and associated with poor prognosis. However, the mechanism underlying the negative effects of neoplastic ICAM-1 remains obscure. Herein, we demonstrate that the survival of NSCLC cells but not normal human bronchial epithelial cells requires an anti-apoptosis signal triggered by fibrinogen γ chain (FGG)–ICAM-1 interaction. ICAM-1–FGG ligation preserves the tyrosine phosphorylation of ICAM-1 cytoplasmic domain and its association with SHP-2, and subsequently promotes Akt and ERK1/2 activation but suppresses JNK and p38 activation. Abolishing ICAM-1–FGG interaction induces NSCLC cell death by activating caspase-9/3 and significantly inhibits tumor development in a mouse xenograft model. Finally, we developed a monoclonal antibody against ICAM-1–FGG binding motif, which blocks ICAM-1‒FGG interaction and effectively suppresses NSCLC cell survival in vitro and tumor growth in vivo. Thus, suppressing ICAM-1–FGG axis provides a potential strategy for NSCLC targeted therapy.