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Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/176712
A unique subset of glycolytic tumour-propagating cells drives squamous cell carcinoma
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Head and neck squamous cell carcinoma (SCC) remains among the most aggressive human cancers. Tumour progression and aggressiveness in SCC are largely driven by tumour-propagating cells (TPCs). Aerobic glycolysis, also known as the Warburg effect, is a characteristic of many cancers; however, whether this adaptation is functionally important in SCC, and at which stage, remains poorly understood. Here, we show that the NAD+-dependent histone deacetylase sirtuin 6 is a robust tumour suppressor in SCC, acting as a modulator of glycolysis in these tumours. Remarkably, rather than a late adaptation, we find enhanced glycolysis specifically in TPCs. More importantly, using single-cell RNA sequencing of TPCs, we identify a subset of TPCs with higher glycolysis and enhanced pentose phosphate pathway and glutathione metabolism, characteristics that are strongly associated with a better antioxidant response. Together, our studies uncover enhanced glycolysis as a main driver in SCC, and, more importantly, identify a subset of TPCs as the cell of origin for the Warburg effect, defining metabolism as a key feature of intra-tumour heterogeneity.
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CHOI, Jee-Eun, et al. A unique subset of glycolytic tumour-propagating cells drives squamous cell carcinoma. Nature Metabolism. 2021. Vol. 3, num. 2, pags. 182-195. ISSN 2522-5812. [consulted: 11 of August of 2026]. Available at: https://hdl.handle.net/2445/176712