Doublecortin-like kinase 1 expression is induced by alternative NF-κB signaling in human lung cancer cells
Doublecortin-like kinase 1 expression is induced by alternative NF-κB signaling in human lung cancer cells
复制标题
双皮质素样激酶 1 表达由人肺癌细胞中的替代 NF-κB 信号传导诱导
DOI：
10.11480/jmds.680005
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发表时间：
2021
影响因子：
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通讯作者：
Haruhiko Sugimura and Yutaka Hata
中科院分区：
文献类型：
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作者：
Yuxiong Lu;Junichi Maruyama;Haruhiko Sugimura and Yutaka Hata
特发性肺纤维化（IPF）是一种病因不明的破坏性纤维化肺病，常与肺癌相关。然而，这种关联的分子机制仍不清楚。我们使用公共数据集分析了IPF肺的基因表达谱，并提取了94个在所有这些中上调的基因。其中，我们确定了DCLK 1，一种众所周知的癌症干细胞标志物。最近的一项研究表明，DCLK 1增强了肺癌细胞中的癌症干细胞样特征。因此，如果在IPF中诱导DCLK 1表达，则其可能是IPF和肺癌之间的分子联系。在这项研究中，我们证实了DCLK 1表达在人类IPF肺和博莱霉素诱导的纤维化小鼠肺中增强。我们还发现，人肺癌H1299细胞表达DCLK 1时，暴露于条件培养基衍生自脂多糖刺激的小鼠巨噬细胞样RAW 264。7个细胞。此外，这种DCLK 1诱导活性对热灭活和蛋白酶K处理敏感。我们还发现IL-17和α-光敏素诱导人肺癌H1299细胞中DCLK 1的表达。此外，RELB沉默，而不是RELA沉默，阻断了条件培养基诱导的DCLK 1表达。因此，抑制替代NF-κB信号传导可能有助于预防IPF肺中的癌症发展。
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.