| First Author | Choi JE | Year | 2021 |
| Journal | Nat Metab | Volume | 3 |
| Issue | 2 | Pages | 182-195 |
| PubMed ID | 33619381 | Mgi Jnum | J:331740 |
| Mgi Id | MGI:7398369 | Doi | 10.1038/s42255-021-00350-6 |
| Citation | Choi JE, et al. (2021) A unique subset of glycolytic tumour-propagating cells drives squamous cell carcinoma. Nat Metab 3(2):182-195 |
| abstractText | 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. |
