The present study investigates roles for NF-kappaB inducing kinase (NIK) in constitutive NF-kappaB activation in lung cancer cells. A wealth of evidence showed that NF-kappaB is often constitutively activated in human cancer cells, including non-small cell lung cancer tissue specimens and cell lines, which may lead to deregulated apoptosis and enhanced resistance of tumor cells to chemotherapy. However, the mechanisms of NF-kappaB activation in lung cancer cells remain largely unknown. We report here that NF-kappaB inducing kinase (NIK) is aberrantly expressed at the pre-translational level in non-small cell lung cancer (NSCLC) cell lines. Depletion of NIK by RNA interference remarkably diminished nuclear NF-kappaB DNA binding activity and reporter gene expression. NIK depletion induced apoptosis in A549 cells, reduced the matrix metalloproteinase 9 (MMP-9) and survivin mRNA expression and affected efficiency of anchorage-independent H1299 cell growth, suggesting a role for NIK in the manifestation of oncogenic phenotype. These results indicate that NIK plays a key role in constitutive NF-kappaB activation in NSCLC cells and implicate NIK as a molecular target for lung cancer therapy. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

PMID: 20338663 [PubMed - as supplied by publisher] Source: National Library of Medicine.