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

Cell Death Dis

State Key Laboratory of Multi-Cell Systems, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, China.

Published: August 2024

AI Article Synopsis

  • ICAM-1 is often overexpressed in non-small cell lung cancer (NSCLC), which is linked to worse patient outcomes, but the reasons for its harmful effects are not fully understood.
  • Research shows that the survival of NSCLC cells relies on a signal from the interaction between fibrinogen γ chain (FGG) and ICAM-1, which activates survival pathways and prevents cell death.
  • By inhibiting the interaction between ICAM-1 and FGG with a developed monoclonal antibody, researchers were able to decrease NSCLC cell survival and tumor growth in experiments, suggesting a new targeted therapy approach for NSCLC.

Article 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11339363PMC
http://dx.doi.org/10.1038/s41419-024-06989-9DOI Listing

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