Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Dig Liver Dis. 2018 Dec;50(12):1353-1361. doi: 10.1016/j.dld.2018.06.011. Epub 2018 Jun 22.
Accumulating evidence has shown the existence of tumor stem cells with therapeutic potential. Previously, we reported that doublecortin like kinase 1 (Dclk1) marks tumor stem cells but not normal stem cells in the intestine of Apc mice, and that Dclk1- and Lgr5-double positive tumor cells are the tumor stem cells of intestinal tumors.
To investigate molecules highly expressed in the Dclk1 normal intestinal and Dclk1 tumor cells in Apc mice.
We used microarray analyses to examine the gene expression profile of Dclk1 cells in both mouse normal intestinal epithelium and Apc mouse intestinal tumors. We also performed immunofluorescence analyses.
Genes related to microtubules and the actin cytoskeleton (e.g., Rac2), and members of the Src family kinases (i.e., Hck, Lyn, Csk, and Ptpn6) were highly expressed in both Dclk1 normal intestinal and Dclk1 tumor cells. Phosphorylated Hck and phosphorylated Lyn were expressed in Lgr5 cells in the intestinal tumors of Lgr5; Apc mice.
We revealed factors that are highly expressed in Dclk1 intestinal tumor cells, which may help to develop cancer stem cell-targeted therapy in future.
越来越多的证据表明存在具有治疗潜力的肿瘤干细胞。此前，我们报道了双皮质激酶 1（Dclk1）标记了 Apc 小鼠肠道中的肿瘤干细胞而非正常干细胞，并且 Dclk1 和 Lgr5 双阳性肿瘤细胞是肠道肿瘤的肿瘤干细胞。
研究 Apc 小鼠中 Dclk1 正常肠细胞和 Dclk1 肿瘤细胞中高度表达的分子。
我们使用微阵列分析来检测 Dclk1 细胞在正常小鼠肠道上皮和 Apc 小鼠肠道肿瘤中的基因表达谱。我们还进行了免疫荧光分析。
与微管和肌动蛋白细胞骨架相关的基因（例如 Rac2）以及Src 家族激酶的成员（即 Hck、Lyn、Csk 和 Ptpn6）在 Dclk1 正常肠细胞和 Dclk1 肿瘤细胞中均高度表达。在 Lgr5;Apc 小鼠的肠道肿瘤中，磷酸化 Hck 和磷酸化 Lyn 表达于 Lgr5 细胞中。
我们揭示了在 Dclk1 肠道肿瘤细胞中高度表达的因子，这可能有助于未来开发针对癌症干细胞的治疗方法。
