Induced focal adhesion kinase expression suppresses apoptosis by activating NF-κB signaling in intestinal epithelial cells

Huifang M. Zhang, Kaspar M. Keledjian, Jaladanki N. Rao, Tongtong Zou, Lan Liu, Bernard S. Marasa, Shelley R. Wang, Lisa Ru, Eric D. Strauch, Jian Ying Wang

Research output: Contribution to journalArticle

Abstract

Focal adhesion kinase (FAK) integrates various extracellular and intracellular signals and is implicated in a variety of biological functions, but its exact role and downstream targeting signals in the regulation of apoptosis in intestinal epithelial cells (IECs) remains unclear. The current study tested the hypothesis that FAK has an antiapoptotic role in the IEC-6 cell line by altering NF-κB signaling. Induced FAK expression by stable transfection with the wild-type (WT)-FAK gene increased FAK phosphorylation, which was associated with an increase in NF-κB activity. These stable WT-FAK-transfected IECs also exhibited increased resistance to apoptosis when they were exposed to TNF-α plus cycloheximide (TNF-α/CHX). Specific inhibition of NF-κB by the recombinant adenoviral vector containing the IκBα superrepressor prevented increased resistance to apoptosis in WT-FAK-transfected cells. In contrast, inactivation of FAK by ectopic expression of dominant-negative mutant of FAK (DNM-FAK) inhibited NF-κB activity and increased the sensitivity to TNF-α/CHX-induced apoptosis. Furthermore, induced expression of endogenous FAK by depletion of cellular polyamines increased NF-κB activity and resulted in increased resistance to TNF-α/CHX-induced apoptosis, both of which were prevented by overexpression of DNM-FAK. These results indicate that increased expression of FAK suppresses TNF-α/CHX-induced apoptosis, at least partially, through the activation of NF-κB signaling in IECs.

Original languageEnglish (US)
Pages (from-to)C1310-C1320
JournalAmerican Journal of Physiology - Cell Physiology
Volume290
Issue number5
DOIs
StatePublished - May 1 2006

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Keywords

  • IκB
  • Polyamines
  • X-linked inhibitor of apoptosis protein
  • α-difluoromethylornithine

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

Cite this

Zhang, H. M., Keledjian, K. M., Rao, J. N., Zou, T., Liu, L., Marasa, B. S., Wang, S. R., Ru, L., Strauch, E. D., & Wang, J. Y. (2006). Induced focal adhesion kinase expression suppresses apoptosis by activating NF-κB signaling in intestinal epithelial cells. American Journal of Physiology - Cell Physiology, 290(5), C1310-C1320. https://doi.org/10.1152/ajpcell.00450.2005