Cancer cells with high expression of CD133 exert FLIP upregulation and resistance to TRAIL-induced apoptosis

Abstract

It is increasingly accepted that cancer stem cells (CSCs) are rather resistant to apoptosis to various inducers, including the immunological apoptogen TRAIL. Here we show that cancer cells with high expression of CD133, a marker that is often associated with CSCs, are resistant to TRAIL-induced apoptosis, compared to their CD133-low counterparts. We show that this resistance can be ascribed to the high expression of FLIP, an inhibitor of the extrinsic apoptotic pathway, in CD133-high cells. Downregulation of FLIP by siRNA in CD133-high cells sensitised them to TRAIL killing. Thus, CD133-high cells may be resistant to TRAIL due to high expression of FLIP.