Cancer stem cells (CSCs) are an uncommon subset of tumor cells capable of self-renewal, differentiating, and recreating the parental tumor when transplanted into the murine background. Over the past two decades, efforts toward understanding CSC biology culminated into identifying a set of signaling pathways sustaining “stemness”. Nevertheless, while metabolic rewiring is nowadays considered a hallmark of cancer, no consensus has been reached on the metabolic features underlying the plastic nature of CSCs, which are capable of residing in a dormant state, and able to rapidly proliferate when the need to repopulate the tumor mass arises. An emerging concept in the field of CSC metabolism is that these cells are extremely reliant on the activity of enzymes involved in lipid metabolism, such as stearoyl-CoA desaturase 1 (SCD1) and 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR). Indeed, SCD1 and HMG-CoAR have been described as key factors for the correct function of a number of concatenated pathways involved in CSC fate decision, such as Hippo and Wnt. In the present review, we describe metabolic futures of CSCs with a special focus on lipid metabolism, which until now represents an underappreciated force in maintaining CSCs and an attractive therapeutic target.
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We thank Tania Merlino for editorial assistance. This work was supported by Italian Association for Cancer Research (AIRC) grant IG17009 to RM, and grant IG15216 to GC, and by Fondo di Ricerca di Ateneo 2014 (C26A142LZ8) and POR FESR Lazio 2007/2013 to RM. MEP is supported by a Fondazione Veronesi fellowship.
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The authors declare that they have no conflict of interest.
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Mancini, R., Noto, A., Pisanu, M.E. et al. Metabolic features of cancer stem cells: the emerging role of lipid metabolism. Oncogene 37, 2367–2378 (2018). https://doi.org/10.1038/s41388-018-0141-3
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