In this study, we investigated whether
proteins that are involved in cytokinesis are potential targets for
therapy of
lung cancer. We find that the
microtubule-associated protein PRC1 (
protein required for cytokinesis 1), which plays a key role in organizing anti-parallel microtubule in the central spindle in cytokinesis, is overexpressed in
lung cancer cell lines compared to normal cells. Increased expression of PRC1 is correlated with a poor prognosis of human
lung adenocarcinoma patients. Lentiviral delivered, inducible RNAi of PRC1 demonstrated that proliferation of
lung cancer cell lines strongly depends on PRC1. Significantly, we also show that PRC1 is required for
tumorigenesis in vivo using a mouse model for
non-small cell lung cancer driven by oncogenic K-RAS and loss of p53. When PRC1 is depleted by in vivo RNA interference, lung
tumor formation is significantly reduced. Although PRC1 has been suggested to regulate Wnt/ß-
catenin signaling in
cancer cells, we find no evidence for a role of PRC1 in this pathway in
lung cancer. Instead, we show that the depletion of PRC1 results in a strong increase in bi- and multinuclear cells due to defects in cytokinesis. This ultimately leads to apoptosis and senescence. Together these data establish PRC1 as a potential target for
therapy of
lung cancer.