Reduced cell proliferation by IKK2 depletion in a mouse lung-cancer model

Abstract

Lung cancer is one of the leading cancer malignancies, with a five-year survival rate of only ∼15%. We have developed a lentiviral-vector-mediated mouse model, which enables generation of non-small-cell lung cancer from less than 100 alveolar epithelial cells, and investigated the role of IKK2 and NF-κB in lung-cancer development. IKK2 depletion in tumour cells significantly attenuated tumour proliferation and significantly prolonged mouse survival. We identified Timp1, one of the NF-κB target genes, as a key mediator for tumour growth. Activation of the Erk signalling pathway and cell proliferation requires Timp-1 and its receptor CD63. Knockdown of either Ikbkb or Timp1 by short hairpin RNAs reduced tumour growth in both xenograft and lentiviral models. Our results thus suggest the possible application of IKK2 and Timp-1 inhibitors in treating lung cancer. Verma and colleagues develop a mouse model to study the role of the NF-κB pathway in lung cancer. They show that depletion of IKK2, a kinase needed for NF-κB activation, inhibits the induction of Timp1. This suppresses the Timp-1-mediated activation of Erk, resulting in decreased tumour-cell proliferation and prolonged survival.

Cite this article

Xia, Y., Yeddula, N., Leblanc, M. et al. Reduced cell proliferation by IKK2 depletion in a mouse lung-cancer model. Nat Cell Biol 14, 257–265 (2012). https://doi.org/10.1038/ncb2428

View full text

>> Full Text:   Reduced cell proliferation by IKK2 depletion in a mouse lung-cancer model