Dear Editor,
According to the cancer stem cell (CSC) hypothesis, cancer cells are organized in a hierarchical manner (Reya et al., 2001). Indeed, the differentiation state of cancer cells has been linked to their proliferative potential, drug response, and ability to metastasize (Clevers, 2011). Targeting self-renewing, undifferentiated cancer cells could therefore be of importance for the success of cancer therapies. A classical case of a tumor composed of undifferentiated and differentiated cells is the tumor induced by pluripotent stem cells (PSCs) (Ben-David and Benvenisty, 2011). We have recently identified several small molecules termed pluripotent-specific inhibitors (PluriSIns) that selectively target undifferentiated tumorigenic PSCs (Ben-David et al., 2013). Several of these compounds, including PluriSIn#1, inhibit the activity of stearoyl-coA desaturase (SCD1) (Ben-David et al., 2013). SCD1 is an endoplasmic reticulum (ER)-membrane protein that plays a key role in the biosynthesis of the mono-unsaturated fatty acid oleate. This novel metabolic vulnerability is in line with the unique metabolome described in PSCs (Panopoulos et al., 2012).
Inhibition of SCD1 was previously suggested as a potential cancer therapy (Hess et al., 2010; Minville-Walz et al., 2010; Roongta et al., 2011); however, why some cancer cells are highly sensitive to SCD1 inhibition, whereas others are completely resistant to it, remains unknown. As undifferentiated human PSCs were highly sensitive to SCD1 inhibition and rapidly lost this sensitivity upon differentiation (Ben-David et al., 2013), and the processes of pluripotency induction and oncogenic transformation share many characteristics (Ben-David and Benvenisty, 2011), we speculated that the sensitivity of some cancer cells to SCD1 inhibition might be related to their differentiation state as well.