Detachment-induced upregulation of XIAP and cIAP2 delays anoikis of intestinal epithelial cells

Z. Liu, H. Li, X. Wu, B. H. Yoo, S. R. Yan, A. W. Stadnyk, T. Sasazuki, S. Shirasawa, E. C. LaCasse, R. G. Korneluk, K. V. Rosen

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Abstract

Detachment of normal epithelial cells from the extracellular matrix triggers apoptosis, a phenomenon called anoikis. Conversely, carcinoma cells tend to be relatively more anoikis-resistant than their normal counterparts, and this increased resistance represents a critical feature of the malignant phenotype. Mechanisms that control susceptibility and resistance to anoikis are not fully understood. It is now known that detachment of non-malignant epithelial cells triggers both pro- and antiapoptotic signals, and it is the balance between these signals and the duration of detachment that determine further fate of the cells. Detachment-induced antiapoptotic events delay anoikis and if cells reattach relatively soon after detachment they survive. Direct regulators of apoptosis responsible for this delay of anoikis are unknown. We found that detachment of non-malignant intestinal epithelial cells triggers upregulation of inhibitors of apoptosis protein (IAP) family, such as X-chromosome-linked inhibitor of apoptosis protein and cellular inhibitor of apoptosis-2 (cIAP2). We demonstrated that this upregulation requires detachment-dependent activation of the transcription factor nuclear factor-κB. We further observed that various IAP antagonists accelerate anoikis, indicating that upregulation of the IAPs delays detachment-triggered apoptosis. We conclude that the IAPs are important regulators of the balance between detachment-triggered life and death signals. Perhaps, not by coincidence, these proteins are often upregulated in carcinomas, tumors composed of cells that tend to be anoikis-resistant.

Original languageEnglish
Pages (from-to)7680-7690
Number of pages11
JournalOncogene
Volume25
Issue number59
DOIs
Publication statusPublished - Dec 14 2006
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Liu, Z., Li, H., Wu, X., Yoo, B. H., Yan, S. R., Stadnyk, A. W., ... Rosen, K. V. (2006). Detachment-induced upregulation of XIAP and cIAP2 delays anoikis of intestinal epithelial cells. Oncogene, 25(59), 7680-7690. https://doi.org/10.1038/sj.onc.1209753