Abstract
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.
Highlights
IntroductionMetastasis is responsible for most of those cancer-related deaths because the spread tumors mostly do not respond to the currently available treatment [1,2,3]
Cancer is one of the leading causes of death in most countries
We first tested if the colon cancer stem cell (CSC) expressed the stearoyl-CoA desaturase 1 (SCD1) enzyme at higher levels by an‐
Summary
Metastasis is responsible for most of those cancer-related deaths because the spread tumors mostly do not respond to the currently available treatment [1,2,3]. Numerous evidences from preclinical and clinical data support that the CSCs are responsible for tumor recurrence after conventional chemotherapy/radiationtherapy and metastasis [2,3,4,5,6]. Many studies have focused on searching for a selective target for CSCs to achieve better outcomes of conventional chemotherapy, radiation therapy, and targeted therapy, only a few are currently under clinical evaluation [6]. The identification of new vulnerable targets for CSCs and the development of therapeutic approaches may be urgently required
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