2026-04-17T17:03:30Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/1767122025-12-04T19:31:38Zcom_2072_1057col_2072_478908col_2072_478917

urn:hdl:2445/176712 A unique subset of glycolytic tumour-propagating cells drives squamous cell carcinoma Choi, Jee-Eun Sebastian, Carlos Ferrer, Christina M. Lewis, Caroline A. Sade Feldman, Moshe LaSalle, Thomas Gonye, Anna Lopez, Begona G. C. Abdelmoula, Walid M. Regan, Michael S. Cetinbas, Murat Pascual, Gloria Wojtkiewicz, Gregory R. Silveira, Giorgia G. Boon, Ruben Ross, Kenneth N. Tirosh, Itary Saladi, Srinivas V. Ellisen, Leif W. Sadreyev, Ruslan I. Aznar Benitah, Salvador Agar, Nathalie Y. R. Hacohen, Nir Mostoslavsky, Raúl Càncer de coll Càncer de cap Proliferació cel·lular Neck cancer Head cancer Cell proliferation 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. 2021-04-26T10:02:42Z 2021-08-22T05:10:20Z 2021-02-22 2021-04-26T08:54:46Z info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion Versió postprint del document publicat a: https://doi.org/10.1038/s42255-021-00350-6 Nature Metabolism, 2021, Vol. 3, num. 2, p. 182-195 https://doi.org/10.1038/s42255-021-00350-6 (c) Springer Nature, 2021 info:eu-repo/semantics/openAccess Springer Nature Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))