Doublecortin-like kinase 1 expression is induced by alternative NF-κB signaling in human lung cancer cells

DOI 機関リポジトリ オープンアクセス
  • Lu Yuxiong
    Department of Medical Biochemistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University
  • Maruyama Junichi
    Department of Medical Biochemistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University
  • Sugimura Haruhiko
    Department of Tumor Pathology, Hamamatsu University School of Medicine
  • Hata Yutaka
    Department of Medical Biochemistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University Center for Brain Integration Research, Tokyo Medical and Dental University

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Idiopathic pulmonary fibrosis (IPF), a devastating fibrotic lung disease of unknown etiology, is frequently associated with lung cancer. However, the molecular mechanism underlying this association remains unclear. We analyzed the gene expression profiles of IPF lungs using public datasets and extracted 94 genes that were upregulated in all of them. Among these, we identified DCLK1, a wellknown cancer stem cell-marker. A recent study revealed that DCLK1 enhances cancer stem cell-like features in lung cancer cells. Therefore, if DCLK1 expression is induced in IPF, it could be a molecular link between IPF and lung cancers. In this study, we confirmed that DCLK1 expression was enhanced in human IPF lungs and in lungs of mice with bleomycin- induced fibrosis. We also found that the human lung cancer H1299 cells expressed DCLK1 when exposed to the conditioned medium derived from the lipopolysaccharide-stimulated murine macrophage- like RAW264.7 cells. Further, this DCLK1-inducing activity was sensitive to heat inactivation and proteinase K treatment. We also revealed that IL17 and lymphotoxin-α induced DCLK1 expression in human lung cancer H1299 cells. Moreover, RELB silencing, but not RELA silencing, blocked the induction of DCLK1 expression by conditioned medium. Hence, the inhibition of alternative NF-κB signaling may be useful to prevent cancer development in IPF lungs.

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