Targeting a Lipid Desaturation Enzyme, SCD1, Selectively Eliminates Colon Cancer Stem Cells through the Suppression of Wnt and NOTCH Signaling

被引:41
|
作者
Yu, Yeongji [1 ]
Kim, Hyejin [1 ]
Choi, SeokGyeong [1 ]
Yu, JinSuh [1 ]
Lee, Joo Yeon [1 ]
Lee, Hani [1 ]
Yoon, Sukjoon [2 ]
Kim, Woo-Young [3 ]
机构
[1] Sookmyung Womens Univ, Coll Pharm, Seoul 04312, South Korea
[2] Sookmyung Womens Univ, Res Inst Womens Hlth, Seoul 04310, South Korea
[3] Sookmyung Womens Univ, Res Inst Pharmaceut Sci, Seoul 04312, South Korea
关键词
CSC; SCD1; monounsaturated fatty acid; NOTCH; Wnt;
D O I
10.3390/cells10010106
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The elimination of the cancer stem cell (CSC) population may be required to achieve better outcomes of cancer therapy. We evaluated stearoyl-CoA desaturase 1 (SCD1) as a novel target for CSC-selective elimination in colon cancer. CSCs expressed more SCD1 than bulk cultured cells (BCCs), and blocking SCD1 expression or function revealed an essential role for SCD1 in the survival of CSCs, but not BCCs. The CSC potential selectively decreased after treatment with the SCD1 inhibitor in vitro and in vivo. The CSC-selective suppression was mediated through the induction of apoptosis. The mechanism leading to selective CSC death was investigated by performing a quantitative RT-PCR analysis of 14 CSC-specific signaling and marker genes after 24 and 48 h of treatment with two concentrations of an inhibitor. The decrease in the expression of Notch1 and AXIN2 preceded changes in the expression of all other genes, at 24 h of treatment in a dose-dependent manner, followed by the downregulation of most Wnt- and NOTCH-signaling genes. Collectively, we showed that not only Wnt but also NOTCH signaling is a primary target of suppression by SCD1 inhibition in CSCs, suggesting the possibility of targeting SCD1 against colon cancer in clinical settings.
引用
收藏
页码:1 / 14
页数:14
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