Dear Editor, According to the cancer stem cell （CSC） hypothesis, cancer ceils are organized in a hierarchical manner （Reya et al, 2001）. Indeed, the differentiation state of cancer cells has been linked to their ...Dear Editor, According to the cancer stem cell （CSC） hypothesis, cancer ceils 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 ceils could therefore be of importance for the success of cancer therapies. A classical case of a tumor composed of undifferenti- ated and differentiated cells is the tumor induced by pluripotent stem cells （PSCs） （Ben-David and Benvenisty, 2011）. We have recently identified several small mole- cules termed pluripotent-specific inhibitors （PluriSIns） that selectively target undif- ferentiated 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）.展开更多
文摘Dear Editor, According to the cancer stem cell （CSC） hypothesis, cancer ceils 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 ceils could therefore be of importance for the success of cancer therapies. A classical case of a tumor composed of undifferenti- ated and differentiated cells is the tumor induced by pluripotent stem cells （PSCs） （Ben-David and Benvenisty, 2011）. We have recently identified several small mole- cules termed pluripotent-specific inhibitors （PluriSIns） that selectively target undif- ferentiated 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）.
